Protein: DNA mismatch repair protein Msh6 (G/T mismatch-binding protein) (GTBP) (GTMBP) (MutS protein homolog 6) (MutS-alpha 160 kDa subunit) (p160) (P54276)
Organism: Mus musculus (Mouse)
Function: 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).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P52701}. Chromosome {ECO:0000250|UniProtKB:P52701}. Note=Associates with H3K36me3 via its PWWP domain. {ECO:0000250|UniProtKB:P52701}.
Sequence: MSRQSTLYSFFPKSPALGDTKKAAAEASRQGAAASGASASRGGDAAWSEAEPGSRSAAVSASSPEAKDLNGGLRRASSSAQAVPPSSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIRKKGKSVRVHVQFFDDSPTRGWVSKRMLKPYTGSKSKEAQKGGHFYSSKSEILRAMQRADEALSKDTAERLQLAVCDEPSEPEEEEETEVHEAYLSDKSEEDNYNESEEEAQPSVQGPRRSSRQVKKRRVISDSESDIGGSDVEFKPDTKQEGSSDDASSGVGDSDSEDLGTFGKGAPKRKRAMVAQGGLRRKSLKKETGSAKRATPILSETKSTLSAFSAPQNSESQTHVSGGGNDSSGPTVWYHETLEWLKPEKRRDEHRRRPDHPEFNPTTLYVPEEFLNSCTPGMRKWWQLKSQNFDLVIFYKVGKFYELYHMDAVIGVSELGLIFMKGNWAHSGFPEIAFGRFSDSLVQKGYKVARVEQTETPEMMEARCRKMAHVSKFDRVVRREICRIITKGTQTYSVLDGDPSENYSRYLLSLKEKEEETSGHTRVYGVCFVDTSLGKFFIGQFSDDRHCSRFRTLVAHYPPVQILFEKGNLSTETKTVLKGSLSSCLQEGLIPGSQFWDATKTLRTLLEGGYFTGNGDSSTVLPLVLKGMTSESDSVGLTPGEESELALSALGGIVFYLKKCLIDQELLSMANFEEYFPLDSDTVSTVKPGAVFTKASQRMVLDAVTLNNLEIFLNGTNGSTEGTLLERLDTCHTPFGKRLLKQWLCAPLCSPSAISDRLDAVEDLMAVPDKVTEVADLLKKLPDLERLLSKIHNVGSPLKSQNHPDSRAIMYEETTYSKKKIIDFLSALEGFKVMCKVSGLLEEVAGGFTSKTLKQVVTLQSKSPKGRFPDLTAELQRWDTAFDHEKARKTGLITPKAGFDSDYDQALADIRENEQSLLEYLDKQRSRLGCKSIVYWGIGRNRYQLEIPENFATRNLPEEYELKSTKKGCKRYWTKTIEKKLANLINAEERRDTSLKDCMRRLFCNFDKNHKDWQSAVECIAVLDVLLCLANYSQGGDGPMCRPEIVLPGEDTHPFLEFKGSRHPCITKTFFGDDFIPNDILIGCEEEAEEHGKAYCVLVTGPNMGGKSTLIRQAGLLAVMAQLGCYVPAEKCRLTPVDRVFTRLGASDRIMSGESTFFVELSETASILRHATAHSLVLVDELGRGTATFDGTAIANAVVKELAETIKCRTLFSTHYHSLVEDYSKSVCVRLGHMACMVENECEDPSQETITFLYKFIKGACPKSYGFNAARLANLPEEVIQKGHRKAREFERMNQSLQLFREVCLATEKPTINGEAIHRLLALINGL
InterPro domains: - IPR036678: MutS, connector domain superfamily (homologous_superfamily) [535-729]
- IPR017261: DNA mismatch repair protein MutS/MSH (family) [3-1350]
- IPR000432: DNA mismatch repair protein MutS, C-terminal (domain) [1125-1321]
- IPR000313: PWWP domain (domain) [90-183]
- IPR007860: DNA mismatch repair protein MutS, connector domain (domain) [537-692]
- IPR045076: DNA mismatch repair MutS (family) [409-1334]
- IPR007696: DNA mismatch repair protein MutS, core (domain) [736-1100]
- IPR007861: DNA mismatch repair protein MutS, clamp (domain) [929-1021]
- IPR036187: DNA mismatch repair protein MutS, core domain superfamily (homologous_superfamily) [733-1065]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [1070-1333]
- IPR007695: DNA mismatch repair protein MutS-like, N-terminal (domain) [406-523]
- IPR016151: DNA mismatch repair protein MutS, N-terminal (homologous_superfamily) [361-530]
Interaction partners: - DNA mismatch repair protein Mlh1
- Mismatch repair endonuclease PMS2
- DNA mismatch repair protein Msh3
- DNA mismatch repair protein Msh2
- Proliferating cell nuclear antigen
- Serine-protein kinase ATM
- MutL homolog 3
- DNA polymerase delta catalytic subunit
- Breast cancer type 1 susceptibility protein homolog
- Exonuclease 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0003677 (DNA binding), GO:0003684 (damaged DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0019953 (sexual reproduction), GO:0044237 (cellular metabolic process), GO:0022412 (cellular process involved in reproduction in multicellular organism), GO:0051321 (meiotic cell cycle), GO:0019222 (regulation of metabolic process), GO:0022402 (cell cycle process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0007049 (cell cycle), GO:0051716 (cellular response to stimulus), GO:0071840 (cellular component organization or biogenesis), GO:1903046 (meiotic cell cycle process), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0032504 (multicellular organism reproduction), GO:0003006 (developmental process involved in reproduction), GO:0048523 (negative regulation of cellular process), GO:0048609 (multicellular organismal reproductive process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0061982 (meiosis I cell cycle process), GO:0007276 (gamete generation), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0007059 (chromosome segregation), GO:1901360 (organic cyclic compound metabolic process), GO:0140013 (meiotic nuclear division), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0007283 (spermatogenesis), GO:0007131 (reciprocal meiotic recombination), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0051246 (regulation of protein metabolic process), GO:0006259 (DNA metabolic process), GO:0006996 (organelle organization), GO:0048232 (male gamete generation), GO:0007127 (meiosis I), GO:0031060 (regulation of histone methylation), GO:0031399 (regulation of protein modification process), GO:0048285 (organelle fission), GO:0006281 (DNA repair), GO:0000280 (nuclear division), GO:0035825 (homologous recombination), GO:0006302 (double-strand break repair), GO:0140527 (reciprocal homologous recombination)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005730 (nucleolus), GO:0005634 (nucleus)