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Protein

DNA mismatch repair protein Msh6

Gene

Msh6

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). 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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1132 – 11398ATPSequence analysis

GO - Molecular functioni

  • ADP binding Source: Ensembl
  • ATPase activity Source: Ensembl
  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: MGI
  • damaged DNA binding Source: MGI
  • DNA binding Source: MGI
  • four-way junction DNA binding Source: GO_Central
  • guanine/thymine mispair binding Source: MGI
  • magnesium ion binding Source: Ensembl
  • methylated histone binding Source: UniProtKB
  • mismatched DNA binding Source: UniProtKB
  • oxidized purine DNA binding Source: Ensembl
  • single base insertion or deletion binding Source: GO_Central
  • single guanine insertion binding Source: Ensembl
  • single thymine insertion binding Source: Ensembl

GO - Biological processi

  • determination of adult lifespan Source: MGI
  • DNA repair Source: MGI
  • intrinsic apoptotic signaling pathway Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • isotype switching Source: MGI
  • maintenance of DNA repeat elements Source: GO_Central
  • meiotic mismatch repair Source: GO_Central
  • mismatch repair Source: MGI
  • negative regulation of DNA recombination Source: MGI
  • positive regulation of helicase activity Source: MGI
  • positive regulation of isotype switching Source: MGI
  • reciprocal meiotic recombination Source: GO_Central
  • response to UV Source: MGI
  • somatic hypermutation of immunoglobulin genes Source: MGI
  • somatic recombination of immunoglobulin gene segments Source: MGI
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh61 Publication
Alternative name(s):
G/T mismatch-binding protein1 Publication
Short name:
GTBPBy similarity
Short name:
GTMBP1 Publication
MutS protein homolog 6By similarity
MutS-alpha 160 kDa subunit
Short name:
p160By similarity
Gene namesi
Name:Msh6Imported
Synonyms:Gtmbp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1343961. Msh6.

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity

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

GO - Cellular componenti

  • cytoplasm Source: MGI
  • Golgi apparatus Source: MGI
  • intracellular membrane-bounded organelle Source: MGI
  • MutSalpha complex Source: MGI
  • nuclear chromatin Source: MGI
  • nucleoplasm Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13581358DNA mismatch repair protein Msh6PRO_0000115208Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141PhosphoserineBy similarity
Modified residuei38 – 381PhosphoserineBy similarity
Modified residuei40 – 401PhosphoserineBy similarity
Modified residuei67 – 671N6-acetyllysineBy similarity
Modified residuei91 – 911PhosphoserineBy similarity
Modified residuei137 – 1371PhosphoserineCombined sources
Modified residuei200 – 2001PhosphoserineBy similarity
Modified residuei219 – 2191PhosphoserineBy similarity
Modified residuei227 – 2271PhosphoserineBy similarity
Modified residuei252 – 2521PhosphoserineCombined sources
Modified residuei254 – 2541PhosphoserineCombined sources
Modified residuei256 – 2561PhosphoserineCombined sources
Modified residuei261 – 2611PhosphoserineCombined sources
Modified residuei269 – 2691PhosphothreonineBy similarity
Modified residuei274 – 2741PhosphoserineBy similarity
Modified residuei275 – 2751PhosphoserineBy similarity
Modified residuei279 – 2791PhosphoserineBy similarity
Modified residuei280 – 2801PhosphoserineBy similarity
Modified residuei487 – 4871PhosphothreonineBy similarity
Modified residuei503 – 5031N6-acetyllysineBy similarity
Modified residuei827 – 8271PhosphoserineBy similarity
Modified residuei932 – 9321PhosphoserineBy similarity
Modified residuei1007 – 10071PhosphothreonineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP54276.
MaxQBiP54276.
PaxDbiP54276.
PeptideAtlasiP54276.
PRIDEiP54276.

PTM databases

iPTMnetiP54276.
PhosphoSiteiP54276.
SwissPalmiP54276.

Expressioni

Gene expression databases

BgeeiENSMUSG00000005370.
CleanExiMM_MSH6.
GenevisibleiP54276. MM.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201528. 8 interactions.
IntActiP54276. 5 interactions.
STRINGi10090.ENSMUSP00000005503.

Structurei

3D structure databases

ProteinModelPortaliP54276.
SMRiP54276. Positions 65-201, 361-1333.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 15463PWWPPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi201 – 2099Poly-Glu

Domaini

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

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated
Contains 1 PWWP domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0217. Eukaryota.
COG0249. LUCA.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiP54276.
KOiK08737.
OMAiALKDCMR.
OrthoDBiEOG091G018J.
TreeFamiTF105842.

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR007695. 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]
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.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P54276-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA
60 70 80 90 100
EPGSRSAAVS ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM
110 120 130 140 150
EGYPWWPCLV YNHPFDGTFI RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP
160 170 180 190 200
YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD EALSKDTAER LQLAVCDEPS
210 220 230 240 250
EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR SSRQVKKRRV
260 270 280 290 300
ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR
310 320 330 340 350
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH
360 370 380 390 400
VSGGGNDSSG PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE
410 420 430 440 450
FLNSCTPGMR KWWQLKSQNF DLVIFYKVGK FYELYHMDAV IGVSELGLIF
460 470 480 490 500
MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA RVEQTETPEM MEARCRKMAH
510 520 530 540 550
VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS LKEKEEETSG
560 570 580 590 600
HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL
610 620 630 640 650
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST
660 670 680 690 700
VLPLVLKGMT SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM
710 720 730 740 750
ANFEEYFPLD SDTVSTVKPG AVFTKASQRM VLDAVTLNNL EIFLNGTNGS
760 770 780 790 800
TEGTLLERLD TCHTPFGKRL LKQWLCAPLC SPSAISDRLD AVEDLMAVPD
810 820 830 840 850
KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI MYEETTYSKK
860 870 880 890 900
KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP
910 920 930 940 950
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE
960 970 980 990 1000
YLDKQRSRLG CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC
1010 1020 1030 1040 1050
KRYWTKTIEK KLANLINAEE RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC
1060 1070 1080 1090 1100
IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG EDTHPFLEFK GSRHPCITKT
1110 1120 1130 1140 1150
FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST LIRQAGLLAV
1160 1170 1180 1190 1200
MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR
1210 1220 1230 1240 1250
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL
1260 1270 1280 1290 1300
VEDYSKSVCV RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA
1310 1320 1330 1340 1350
ARLANLPEEV IQKGHRKARE FERMNQSLQL FREVCLATEK PTINGEAIHR

LLALINGL
Length:1,358
Mass (Da):151,084
Last modified:July 27, 2011 - v3
Checksum:i979D289BC69E6047
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 662EA → DG in AAC53034 (PubMed:8812455).Curated
Sequence conflicti374 – 3752PE → QK in AAC53034 (PubMed:8812455).Curated
Sequence conflicti754 – 7541T → N in AAC53034 (PubMed:8812455).Curated
Sequence conflicti800 – 8001D → Y in AAC53034 (PubMed:8812455).Curated
Sequence conflicti1227 – 12271N → S in AAC53034 (PubMed:8812455).Curated
Sequence conflicti1329 – 13291Q → R in AAC53034 (PubMed:8812455).Curated
Sequence conflicti1333 – 13331E → G in AAC53034 (PubMed:8812455).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29021.1.
RefSeqiNP_034960.1. NM_010830.2.
UniGeneiMm.18210.

Genome annotation databases

EnsembliENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370.
GeneIDi17688.
KEGGimmu:17688.
UCSCiuc008dvd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29021.1.
RefSeqiNP_034960.1. NM_010830.2.
UniGeneiMm.18210.

3D structure databases

ProteinModelPortaliP54276.
SMRiP54276. Positions 65-201, 361-1333.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201528. 8 interactions.
IntActiP54276. 5 interactions.
STRINGi10090.ENSMUSP00000005503.

PTM databases

iPTMnetiP54276.
PhosphoSiteiP54276.
SwissPalmiP54276.

Proteomic databases

EPDiP54276.
MaxQBiP54276.
PaxDbiP54276.
PeptideAtlasiP54276.
PRIDEiP54276.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370.
GeneIDi17688.
KEGGimmu:17688.
UCSCiuc008dvd.2. mouse.

Organism-specific databases

CTDi2956.
MGIiMGI:1343961. Msh6.

Phylogenomic databases

eggNOGiKOG0217. Eukaryota.
COG0249. LUCA.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiP54276.
KOiK08737.
OMAiALKDCMR.
OrthoDBiEOG091G018J.
TreeFamiTF105842.

Enzyme and pathway databases

ReactomeiR-MMU-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).

Miscellaneous databases

ChiTaRSiMsh6. mouse.
PROiP54276.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005370.
CleanExiMM_MSH6.
GenevisibleiP54276. MM.

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR007695. 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]
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.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMSH6_MOUSE
AccessioniPrimary (citable) accession number: P54276
Secondary accession number(s): O54710, Q6GTK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 126 of the entry and version 3 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

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.