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P54276

- MSH6_MOUSE

UniProt

P54276 - MSH6_MOUSE

Protein

DNA mismatch repair protein Msh6

Gene

Msh6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 3 (27 Jul 2011)
      Previous versions | rss
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    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: RefGenome
    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

    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

    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

    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.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.
    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

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    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

    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:
    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

    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: October 1, 2014
    This is version 108 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