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P54276 - MSH6_MOUSE

UniProt

P54276 - MSH6_MOUSE

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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

  1. ADP binding Source: Ensembl
  2. ATP binding Source: UniProtKB-KW
  3. chromatin binding Source: MGI
  4. damaged DNA binding Source: MGI
  5. DNA binding Source: MGI
  6. DNA-dependent ATPase activity Source: GO_Central
  7. four-way junction DNA binding Source: GO_Central
  8. guanine/thymine mispair binding Source: MGI
  9. magnesium ion binding Source: Ensembl
  10. methylated histone binding Source: UniProtKB
  11. mismatched DNA binding Source: UniProtKB
  12. oxidized purine DNA binding Source: Ensembl
  13. single base insertion or deletion binding Source: GO_Central
  14. single guanine insertion binding Source: Ensembl
  15. single thymine insertion binding Source: Ensembl

GO - Biological processi

  1. ATP catabolic process Source: MGI
  2. determination of adult lifespan Source: MGI
  3. DNA repair Source: MGI
  4. intrinsic apoptotic signaling pathway Source: MGI
  5. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  6. isotype switching Source: MGI
  7. maintenance of DNA repeat elements Source: GO_Central
  8. meiotic mismatch repair Source: GO_Central
  9. mismatch repair Source: MGI
  10. negative regulation of DNA recombination Source: MGI
  11. positive regulation of helicase activity Source: MGI
  12. reciprocal meiotic recombination Source: GO_Central
  13. response to UV Source: MGI
  14. somatic hypermutation of immunoglobulin genes Source: MGI
  15. 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

ReactomeiREACT_240368. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Msh6
Synonyms:Gtmbp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus
ProteomesiUP000000589: 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

  1. cytoplasm Source: MGI
  2. Golgi apparatus Source: MGI
  3. intracellular membrane-bounded organelle Source: MGI
  4. MutSalpha complex Source: MGI
  5. nuclear chromatin Source: MGI
  6. nucleus Source: MGI
  7. 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 – 1371PhosphoserineBy similarity
Modified residuei200 – 2001PhosphoserineBy similarity
Modified residuei219 – 2191PhosphoserineBy similarity
Modified residuei227 – 2271PhosphoserineBy similarity
Modified residuei252 – 2521PhosphoserineBy similarity
Modified residuei254 – 2541PhosphoserineBy similarity
Modified residuei256 – 2561PhosphoserineBy similarity
Modified residuei261 – 2611Phosphoserine1 Publication
Modified residuei269 – 2691PhosphothreonineBy similarity
Modified residuei274 – 2741PhosphoserineBy similarity
Modified residuei275 – 2751PhosphoserineBy similarity
Modified residuei279 – 2791PhosphoserineBy similarity
Modified residuei280 – 2801PhosphoserineBy similarity
Modified residuei503 – 5031N6-acetyllysineBy similarity
Modified residuei827 – 8271PhosphoserineBy 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

MaxQBiP54276.
PaxDbiP54276.
PRIDEiP54276.

PTM databases

PhosphoSiteiP54276.

Expressioni

Gene expression databases

BgeeiP54276.
CleanExiMM_MSH6.
ExpressionAtlasiP54276. baseline and differential.
GenevestigatoriP54276.

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

Protein-protein interaction databases

BioGridi201528. 5 interactions.
IntActiP54276. 5 interactions.

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

eggNOGiCOG0249.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiP54276.
KOiK08737.
OMAiALKDCMR.
OrthoDBiEOG7K9K27.
TreeFamiTF105842.

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR017261. 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]
PANTHERiPTHR11361:SF31. PTHR11361:SF31. 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.
PF00855. PWWP. 1 hit.
[Graphical view]
PIRSFiPIRSF037677. DNA_mis_repair_Msh6. 1 hit.
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. 5 interactions.
IntActiP54276. 5 interactions.

PTM databases

PhosphoSiteiP54276.

Proteomic databases

MaxQBiP54276.
PaxDbiP54276.
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

eggNOGiCOG0249.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiP54276.
KOiK08737.
OMAiALKDCMR.
OrthoDBiEOG7K9K27.
TreeFamiTF105842.

Enzyme and pathway databases

ReactomeiREACT_240368. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).

Miscellaneous databases

ChiTaRSiMsh6. mouse.
NextBioi292264.
PROiP54276.
SOURCEiSearch...

Gene expression databases

BgeeiP54276.
CleanExiMM_MSH6.
ExpressionAtlasiP54276. baseline and differential.
GenevestigatoriP54276.

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR017261. 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]
PANTHERiPTHR11361:SF31. PTHR11361:SF31. 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.
PF00855. PWWP. 1 hit.
[Graphical view]
PIRSFiPIRSF037677. DNA_mis_repair_Msh6. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
+Additional computationally mapped references.

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: February 4, 2015
This is version 112 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

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.