UniProtKB - P54276 (MSH6_MOUSE)
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Protein
DNA mismatch repair protein Msh6
Gene
Msh6
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1132 – 1139 | ATPSequence analysis | 8 |
GO - Molecular functioni
- ADP binding Source: Ensembl
- ATP binding Source: UniProtKB-KW
- chromatin binding Source: MGI
- damaged DNA binding Source: MGI
- DNA binding Source: MGI
- DNA-dependent ATPase activity Source: GO_Central
- 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
- MutLalpha complex binding Source: Ensembl
- 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
- 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
- response to UV Source: MGI
- somatic hypermutation of immunoglobulin genes Source: MGI
- somatic recombination of immunoglobulin gene segments Source: MGI
Keywordsi
Molecular function | DNA-binding |
Biological process | DNA damage, DNA repair |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). |
Names & Taxonomyi
Protein namesi | Recommended name: DNA mismatch repair protein Msh61 PublicationAlternative 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 | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1343961. Msh6. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000115208 | 1 – 1358 | DNA mismatch repair protein Msh6Add BLAST | 1358 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 14 | PhosphoserineBy similarity | 1 | |
Modified residuei | 38 | PhosphoserineBy similarity | 1 | |
Modified residuei | 40 | PhosphoserineBy similarity | 1 | |
Modified residuei | 67 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 91 | PhosphoserineBy similarity | 1 | |
Modified residuei | 137 | PhosphoserineCombined sources | 1 | |
Modified residuei | 200 | PhosphoserineBy similarity | 1 | |
Modified residuei | 219 | PhosphoserineBy similarity | 1 | |
Modified residuei | 227 | PhosphoserineBy similarity | 1 | |
Modified residuei | 252 | PhosphoserineCombined sources | 1 | |
Modified residuei | 254 | PhosphoserineCombined sources | 1 | |
Modified residuei | 256 | PhosphoserineCombined sources | 1 | |
Modified residuei | 261 | PhosphoserineCombined sources | 1 | |
Modified residuei | 269 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 274 | PhosphoserineBy similarity | 1 | |
Modified residuei | 275 | PhosphoserineBy similarity | 1 | |
Modified residuei | 279 | PhosphoserineBy similarity | 1 | |
Modified residuei | 280 | PhosphoserineBy similarity | 1 | |
Modified residuei | 487 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 503 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 827 | PhosphoserineBy similarity | 1 | |
Modified residuei | 932 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1007 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P54276. |
MaxQBi | P54276. |
PaxDbi | P54276. |
PeptideAtlasi | P54276. |
PRIDEi | P54276. |
PTM databases
iPTMneti | P54276. |
PhosphoSitePlusi | P54276. |
SwissPalmi | P54276. |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000005370. |
CleanExi | MM_MSH6. |
Genevisiblei | P54276. 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
- methylated histone binding Source: UniProtKB
- MutLalpha complex binding Source: Ensembl
Protein-protein interaction databases
BioGridi | 201528. 9 interactors. |
CORUMi | P54276. |
IntActi | P54276. 5 interactors. |
MINTi | P54276. |
STRINGi | 10090.ENSMUSP00000005503. |
Structurei
3D structure databases
ProteinModelPortali | P54276. |
SMRi | P54276. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 92 – 154 | PWWPPROSITE-ProRule annotationAdd BLAST | 63 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 201 – 209 | Poly-Glu | 9 |
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
Phylogenomic databases
eggNOGi | KOG0217. Eukaryota. COG0249. LUCA. |
GeneTreei | ENSGT00550000075024. |
HOGENOMi | HOG000243127. |
HOVERGENi | HBG000101. |
InParanoidi | P54276. |
KOi | K08737. |
OMAi | TPMMAQY. |
OrthoDBi | EOG091G018J. |
TreeFami | TF105842. |
Family and domain databases
Gene3Di | 3.30.420.110. 1 hit. 3.40.1170.10. 1 hit. |
InterProi | View 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. IPR000313. PWWP_dom. |
PANTHERi | PTHR11361:SF31. PTHR11361:SF31. 1 hit. |
Pfami | View 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. PF00855. PWWP. 1 hit. |
PIRSFi | PIRSF037677. DNA_mis_repair_Msh6. 1 hit. |
SMARTi | View protein in SMART SM00534. MUTSac. 1 hit. SM00533. MUTSd. 1 hit. SM00293. PWWP. 1 hit. |
SUPFAMi | SSF48334. SSF48334. 1 hit. SSF52540. SSF52540. 1 hit. SSF55271. SSF55271. 1 hit. |
PROSITEi | View protein in PROSITE PS00486. DNA_MISMATCH_REPAIR_2. 1 hit. PS50812. PWWP. 1 hit. |
i Sequence
Sequence statusi: Complete.
P54276-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 65 – 66 | EA → DG in AAC53034 (PubMed:8812455).Curated | 2 | |
Sequence conflicti | 374 – 375 | PE → QK in AAC53034 (PubMed:8812455).Curated | 2 | |
Sequence conflicti | 754 | T → N in AAC53034 (PubMed:8812455).Curated | 1 | |
Sequence conflicti | 800 | D → Y in AAC53034 (PubMed:8812455).Curated | 1 | |
Sequence conflicti | 1227 | N → S in AAC53034 (PubMed:8812455).Curated | 1 | |
Sequence conflicti | 1329 | Q → R in AAC53034 (PubMed:8812455).Curated | 1 | |
Sequence conflicti | 1333 | E → G in AAC53034 (PubMed:8812455).Curated | 1 |
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. |
CCDSi | CCDS29021.1. |
RefSeqi | NP_034960.1. NM_010830.2. |
UniGenei | Mm.18210. |
Genome annotation databases
Ensembli | ENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370. |
GeneIDi | 17688. |
KEGGi | mmu:17688. |
UCSCi | uc008dvd.2. mouse. |
Similar proteinsi
Entry informationi
Entry namei | MSH6_MOUSE | |
Accessioni | P54276Primary (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 28, 2018 | |
This is version 138 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |