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P54276

- MSH6_MOUSE

UniProt

P54276 - MSH6_MOUSE

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Protein
DNA mismatch repair protein Msh6
Gene
Msh6, Gtmbp
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1132 – 11398ATP Reviewed prediction

GO - Molecular functioni

  1. ADP binding Source: Ensembl
  2. ATP binding Source: UniProtKB-KW
  3. DNA binding Source: MGI
  4. DNA-dependent ATPase activity Source: RefGenome
  5. chromatin binding Source: MGI
  6. damaged DNA binding Source: MGI
  7. four-way junction DNA binding Source: RefGenome
  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: RefGenome
  14. single guanine insertion binding Source: Ensembl
  15. single thymine insertion binding Source: Ensembl

GO - Biological processi

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

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
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. MutSalpha complex Source: MGI
  2. nuclear chromatin 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 Msh6
PRO_0000115208Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141Phosphoserine By similarity
Modified residuei38 – 381Phosphoserine By similarity
Modified residuei40 – 401Phosphoserine By similarity
Modified residuei67 – 671N6-acetyllysine By similarity
Modified residuei91 – 911Phosphoserine By similarity
Modified residuei137 – 1371Phosphoserine By similarity
Modified residuei200 – 2001Phosphoserine By similarity
Modified residuei219 – 2191Phosphoserine By similarity
Modified residuei227 – 2271Phosphoserine By similarity
Modified residuei252 – 2521Phosphoserine By similarity
Modified residuei254 – 2541Phosphoserine By similarity
Modified residuei256 – 2561Phosphoserine By similarity
Modified residuei261 – 2611Phosphoserine1 Publication
Modified residuei269 – 2691Phosphothreonine By similarity
Modified residuei274 – 2741Phosphoserine By similarity
Modified residuei275 – 2751Phosphoserine By similarity
Modified residuei279 – 2791Phosphoserine By similarity
Modified residuei280 – 2801Phosphoserine By similarity
Modified residuei503 – 5031N6-acetyllysine By similarity
Modified residuei827 – 8271Phosphoserine By 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

ArrayExpressiP54276.
BgeeiP54276.
CleanExiMM_MSH6.
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.

Protein-protein interaction databases

BioGridi201528. 5 interactions.
IntActiP54276. 5 interactions.

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 15463PWWP
Add
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

Contains 1 PWWP domain.

Phylogenomic databases

eggNOGiCOG0249.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiQ6GTK8.
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

MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA     50
EPGSRSAAVS ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM 100
EGYPWWPCLV YNHPFDGTFI RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP 150
YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD EALSKDTAER LQLAVCDEPS 200
EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR SSRQVKKRRV 250
ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR 300
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH 350
VSGGGNDSSG PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE 400
FLNSCTPGMR KWWQLKSQNF DLVIFYKVGK FYELYHMDAV IGVSELGLIF 450
MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA RVEQTETPEM MEARCRKMAH 500
VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS LKEKEEETSG 550
HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL 600
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST 650
VLPLVLKGMT SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM 700
ANFEEYFPLD SDTVSTVKPG AVFTKASQRM VLDAVTLNNL EIFLNGTNGS 750
TEGTLLERLD TCHTPFGKRL LKQWLCAPLC SPSAISDRLD AVEDLMAVPD 800
KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI MYEETTYSKK 850
KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP 900
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE 950
YLDKQRSRLG CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC 1000
KRYWTKTIEK KLANLINAEE RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC 1050
IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG EDTHPFLEFK GSRHPCITKT 1100
FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST LIRQAGLLAV 1150
MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR 1200
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL 1250
VEDYSKSVCV RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA 1300
ARLANLPEEV IQKGHRKARE FERMNQSLQL FREVCLATEK PTINGEAIHR 1350
LLALINGL 1358
Length:1,358
Mass (Da):151,084
Last modified:July 27, 2011 - v3
Checksum:i979D289BC69E6047
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 662EA → DG in AAC53034. 1 Publication
Sequence conflicti374 – 3752PE → QK in AAC53034. 1 Publication
Sequence conflicti754 – 7541T → N in AAC53034. 1 Publication
Sequence conflicti800 – 8001D → Y in AAC53034. 1 Publication
Sequence conflicti1227 – 12271N → S in AAC53034. 1 Publication
Sequence conflicti1329 – 13291Q → R in AAC53034. 1 Publication
Sequence conflicti1333 – 13331E → G in AAC53034. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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.

3D structure databases

ProteinModelPortali P54276.
SMRi P54276. Positions 65-201, 361-1333.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201528. 5 interactions.
IntActi P54276. 5 interactions.

PTM databases

PhosphoSitei P54276.

Proteomic databases

MaxQBi P54276.
PaxDbi P54276.
PRIDEi P54276.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000005503 ; ENSMUSP00000005503 ; ENSMUSG00000005370 .
GeneIDi 17688.
KEGGi mmu:17688.
UCSCi uc008dvd.2. mouse.

Organism-specific databases

CTDi 2956.
MGIi MGI:1343961. Msh6.

Phylogenomic databases

eggNOGi COG0249.
GeneTreei ENSGT00550000075024.
HOGENOMi HOG000243127.
HOVERGENi HBG000101.
InParanoidi Q6GTK8.
KOi K08737.
OMAi ALKDCMR.
OrthoDBi EOG7K9K27.
TreeFami TF105842.

Miscellaneous databases

ChiTaRSi MSH6. mouse.
NextBioi 292264.
PROi P54276.
SOURCEi Search...

Gene expression databases

ArrayExpressi P54276.
Bgeei P54276.
CleanExi MM_MSH6.
Genevestigatori P54276.

Family and domain databases

Gene3Di 3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProi IPR017261. 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 ]
PANTHERi PTHR11361:SF31. PTHR11361:SF31. 1 hit.
Pfami 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.
[Graphical view ]
PIRSFi PIRSF037677. DNA_mis_repair_Msh6. 1 hit.
SMARTi SM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view ]
SUPFAMi SSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEi PS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view ]
ProtoNeti Search...

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.

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: July 9, 2014
This is version 107 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

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