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Protein

DNA mismatch repair protein Msh6

Gene

Msh6

Organism
Mus musculus (Mouse)
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. 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)DescriptionActionsGraphical viewLength
Nucleotide bindingi1132 – 1139ATPSequence analysis8

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 functionDNA-binding
Biological processDNA damage, DNA repair
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1343961 Msh6

Subcellular locationi

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

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001152081 – 1358DNA mismatch repair protein Msh6Add BLAST1358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineBy similarity1
Modified residuei38PhosphoserineBy similarity1
Modified residuei40PhosphoserineBy similarity1
Modified residuei67N6-acetyllysineBy similarity1
Modified residuei91PhosphoserineBy similarity1
Modified residuei137PhosphoserineCombined sources1
Modified residuei200PhosphoserineBy similarity1
Modified residuei219PhosphoserineBy similarity1
Modified residuei227PhosphoserineBy similarity1
Modified residuei252PhosphoserineCombined sources1
Modified residuei254PhosphoserineCombined sources1
Modified residuei256PhosphoserineCombined sources1
Modified residuei261PhosphoserineCombined sources1
Modified residuei269PhosphothreonineBy similarity1
Modified residuei274PhosphoserineBy similarity1
Modified residuei275PhosphoserineBy similarity1
Modified residuei279PhosphoserineBy similarity1
Modified residuei280PhosphoserineBy similarity1
Modified residuei487PhosphothreonineBy similarity1
Modified residuei503N6-acetyllysineBy similarity1
Modified residuei827PhosphoserineBy similarity1
Modified residuei932PhosphoserineBy similarity1
Modified residuei1007PhosphothreonineBy similarity1

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
PhosphoSitePlusiP54276
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, 9 interactors
ComplexPortaliCPX-81 DNA mismatch repair MutSalpha complex
CORUMiP54276
IntActiP54276, 5 interactors
MINTiP54276
STRINGi10090.ENSMUSP00000005503

Structurei

3D structure databases

ProteinModelPortaliP54276
SMRiP54276
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 154PWWPPROSITE-ProRule annotationAdd BLAST63

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi201 – 209Poly-Glu9

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

eggNOGiKOG0217 Eukaryota
COG0249 LUCA
GeneTreeiENSGT00550000075024
HOGENOMiHOG000243127
HOVERGENiHBG000101
InParanoidiP54276
KOiK08737
OMAiTPMMAQY
OrthoDBiEOG091G018J
TreeFamiTF105842

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
IPR000313 PWWP_dom
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
PF00855 PWWP, 1 hit
PIRSFiPIRSF037677 DNA_mis_repair_Msh6, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SM00293 PWWP, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
SSF55271 SSF55271, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit
PS50812 PWWP, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti65 – 66EA → DG in AAC53034 (PubMed:8812455).Curated2
Sequence conflicti374 – 375PE → QK in AAC53034 (PubMed:8812455).Curated2
Sequence conflicti754T → N in AAC53034 (PubMed:8812455).Curated1
Sequence conflicti800D → Y in AAC53034 (PubMed:8812455).Curated1
Sequence conflicti1227N → S in AAC53034 (PubMed:8812455).Curated1
Sequence conflicti1329Q → R in AAC53034 (PubMed:8812455).Curated1
Sequence conflicti1333E → G in AAC53034 (PubMed:8812455).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiMSH6_MOUSE
AccessioniPrimary (citable) accession number: P54276
Secondary accession number(s): O54710, Q6GTK8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 139 of the entry and version 3 of the sequence. See 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

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