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P54276 (MSH6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. 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 Msh6
Alternative name(s):
G/T mismatch-binding protein
Short name=GTBP
Short name=GTMBP
MutS-alpha 160 kDa subunit
p160
Gene names
Name:Msh6
Synonyms:Gtmbp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1358 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. 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 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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction By similarity.

Subunit structure

Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms 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 By similarity.

Subcellular location

Nucleus By similarity. Chromosome By similarity. Note: Associates with H3K36me3 via its PWWP domain By similarity.

Domain

The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) By similarity.

Post-translational modification

Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway By similarity.

Sequence similarities

Belongs to the DNA mismatch repair MutS family.

Contains 1 PWWP domain.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentChromosome
Nucleus
   LigandATP-binding
DNA-binding
Nucleotide-binding
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdetermination of adult lifespan

Inferred from mutant phenotype PubMed 10545954Ref.2. Source: MGI

intrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 14632208. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype PubMed 15324697. Source: MGI

isotype switching

Inferred from mutant phenotype PubMed 16618598. Source: MGI

maintenance of DNA repeat elements

Inferred from Biological aspect of Ancestor. Source: RefGenome

meiotic mismatch repair

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatch repair

Inferred from mutant phenotype PubMed 12370835PubMed 15324697PubMed 16728433Ref.2. Source: MGI

negative regulation of DNA recombination

Inferred from mutant phenotype PubMed 10545954. Source: MGI

positive regulation of helicase activity

Inferred from electronic annotation. Source: Ensembl

reciprocal meiotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to UV

Inferred from mutant phenotype PubMed 14632208. Source: MGI

somatic hypermutation of immunoglobulin genes

Inferred from mutant phenotype PubMed 10662804PubMed 15238604PubMed 16618598. Source: MGI

somatic recombination of immunoglobulin gene segments

Inferred from mutant phenotype PubMed 15238604. Source: MGI

   Cellular_componentMutSalpha complex

Inferred from direct assay PubMed 16713580. Source: MGI

nuclear chromatin

Inferred from direct assay PubMed 16618598. Source: MGI

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from mutant phenotype PubMed 10545954. Source: MGI

DNA-dependent ATPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

chromatin binding

Inferred from direct assay PubMed 16618598. Source: MGI

damaged DNA binding

Inferred from mutant phenotype PubMed 10545954. Source: MGI

four-way junction DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

guanine/thymine mispair binding

Inferred from direct assay PubMed 15324697. Source: MGI

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

methylated histone binding

Inferred from sequence or structural similarity. Source: UniProtKB

mismatched DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

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

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13581358DNA mismatch repair protein Msh6
PRO_0000115208

Regions

Domain92 – 15463PWWP
Nucleotide binding1132 – 11398ATP Potential
Compositional bias201 – 2099Poly-Glu

Amino acid modifications

Modified residue141Phosphoserine By similarity
Modified residue381Phosphoserine By similarity
Modified residue401Phosphoserine By similarity
Modified residue671N6-acetyllysine By similarity
Modified residue911Phosphoserine By similarity
Modified residue1371Phosphoserine By similarity
Modified residue2001Phosphoserine By similarity
Modified residue2191Phosphoserine By similarity
Modified residue2271Phosphoserine By similarity
Modified residue2521Phosphoserine By similarity
Modified residue2541Phosphoserine By similarity
Modified residue2561Phosphoserine By similarity
Modified residue2611Phosphoserine Ref.5
Modified residue2691Phosphothreonine By similarity
Modified residue2741Phosphoserine By similarity
Modified residue2751Phosphoserine By similarity
Modified residue2791Phosphoserine By similarity
Modified residue2801Phosphoserine By similarity
Modified residue5031N6-acetyllysine By similarity
Modified residue8271Phosphoserine By similarity

Experimental info

Sequence conflict65 – 662EA → DG in AAC53034. Ref.1
Sequence conflict374 – 3752PE → QK in AAC53034. Ref.1
Sequence conflict7541T → N in AAC53034. Ref.1
Sequence conflict8001D → Y in AAC53034. Ref.1
Sequence conflict12271N → S in AAC53034. Ref.1
Sequence conflict13291Q → R in AAC53034. Ref.1
Sequence conflict13331E → G in AAC53034. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P54276 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 979D289BC69E6047

FASTA1,358151,084
        10         20         30         40         50         60 
MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA EPGSRSAAVS 

        70         80         90        100        110        120 
ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI 

       130        140        150        160        170        180 
RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD 

       190        200        210        220        230        240 
EALSKDTAER LQLAVCDEPS EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR 

       250        260        270        280        290        300 
SSRQVKKRRV ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR 

       310        320        330        340        350        360 
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH VSGGGNDSSG 

       370        380        390        400        410        420 
PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE FLNSCTPGMR KWWQLKSQNF 

       430        440        450        460        470        480 
DLVIFYKVGK FYELYHMDAV IGVSELGLIF MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA 

       490        500        510        520        530        540 
RVEQTETPEM MEARCRKMAH VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS 

       550        560        570        580        590        600 
LKEKEEETSG HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL 

       610        620        630        640        650        660 
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST VLPLVLKGMT 

       670        680        690        700        710        720 
SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM ANFEEYFPLD SDTVSTVKPG 

       730        740        750        760        770        780 
AVFTKASQRM VLDAVTLNNL EIFLNGTNGS TEGTLLERLD TCHTPFGKRL LKQWLCAPLC 

       790        800        810        820        830        840 
SPSAISDRLD AVEDLMAVPD KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI 

       850        860        870        880        890        900 
MYEETTYSKK KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP 

       910        920        930        940        950        960 
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE YLDKQRSRLG 

       970        980        990       1000       1010       1020 
CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC KRYWTKTIEK KLANLINAEE 

      1030       1040       1050       1060       1070       1080 
RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG 

      1090       1100       1110       1120       1130       1140 
EDTHPFLEFK GSRHPCITKT FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST 

      1150       1160       1170       1180       1190       1200 
LIRQAGLLAV MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR 

      1210       1220       1230       1240       1250       1260 
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL VEDYSKSVCV 

      1270       1280       1290       1300       1310       1320 
RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA ARLANLPEEV IQKGHRKARE 

      1330       1340       1350 
FERMNQSLQL FREVCLATEK PTINGEAIHR LLALINGL 

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene."
Corradi A., Croci L., Stayton C.L., Gulisano M., Boncinelli E., Consalez G.G.
Genomics 36:288-295(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Mutation in the mismatch repair gene Msh6 causes cancer susceptibility."
Edelmann W., Yang K., Umar A., Heyer J., Lau K., Fan K., Liedtke W., Cohen P., Kane M.K., Lipford J.R., Yu N., Crouse G.F., Pollard J.W., Kunkel T., Lipkin M., Kolodner R., Kucherlapati R.
Cell 91:467-477(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/Ola.
[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 tumor.
[4]Donohue P.J., Feng S.L.Y., Alberts G.F., Guo Y., Peifley K.A., Hsu D.K.W., Winkles J.A.
Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 375-425 AND 1001-1050.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U42190 mRNA. Translation: AAC53034.1.
AF031087, AF031085, AF031086 Genomic DNA. Translation: AAB88445.1.
BC051160 mRNA. Translation: AAH51160.1.
BC051634 mRNA. Translation: AAH51634.1.
U61388 mRNA. Translation: AAB39930.1.
U61389 mRNA. Translation: AAB39931.1.
CCDSCCDS29021.1.
RefSeqNP_034960.1. NM_010830.2.
UniGeneMm.18210.

3D structure databases

ProteinModelPortalP54276.
SMRP54276. Positions 65-201, 361-1333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201528. 5 interactions.
IntActP54276. 5 interactions.

PTM databases

PhosphoSiteP54276.

Proteomic databases

MaxQBP54276.
PaxDbP54276.
PRIDEP54276.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370.
GeneID17688.
KEGGmmu:17688.
UCSCuc008dvd.2. mouse.

Organism-specific databases

CTD2956.
MGIMGI:1343961. Msh6.

Phylogenomic databases

eggNOGCOG0249.
GeneTreeENSGT00550000075024.
HOGENOMHOG000243127.
HOVERGENHBG000101.
InParanoidQ6GTK8.
KOK08737.
OMAALKDCMR.
OrthoDBEOG7K9K27.
TreeFamTF105842.

Gene expression databases

ArrayExpressP54276.
BgeeP54276.
CleanExMM_MSH6.
GenevestigatorP54276.

Family and domain databases

Gene3D3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProIPR017261. DNA_mismatch_repair_Msh6.
IPR015536. DNA_mismatch_repair_MSH6_C.
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.
IPR016151. DNA_mismatch_repair_MutS_N.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
IPR027417. P-loop_NTPase.
IPR000313. PWWP_dom.
[Graphical view]
PANTHERPTHR11361:SF31. PTHR11361:SF31. 1 hit.
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.
PF00855. PWWP. 1 hit.
[Graphical view]
PIRSFPIRSF037677. DNA_mis_repair_Msh6. 1 hit.
SMARTSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMSH6. mouse.
NextBio292264.
PROP54276.
SOURCESearch...

Entry information

Entry nameMSH6_MOUSE
AccessionPrimary (citable) accession number: P54276
Secondary accession number(s): O54710, Q6GTK8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 107 of the entry and version 3 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