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Msh6 |
Protein FULL name:
DNA mismatch repair protein Msh6 [Mus musculus].
Msh6 (Mus musculus) is product of expression of Msh6 gene.
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 (By similarity).
SUBUNIT: 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).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity).
SIMILARITY: Belongs to the DNA mismatch repair mutS family.
SIMILARITY: Contains 1 PWWP domain.
| NCBI GenPept GI number(s): |
6754744 |
| Species: | Mus musculus |
Links to other databases:
| Database | ID | Link |
| Uniprot | P54276 |
P54276 |
| PFAM: | - |
P54276 (Link - using uniprot id) |
| InterPro: | - |
P54276 (Link - using uniprot id) |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MSRQSTLYSFFPKSPALGDTKKAAAEASRQGAAASGASASRGGDAAWSEA EPGSRSAAVSASSPEAKDLNGGLRRASSSAQAVPPSSCDFSPGDLVWAKM EGYPWWPCLVYNHPFDGTFIRKKGKSVRVHVQFFDDSPTRGWVSKRMLKP YTGSKSKEAQKGGHFYSSKSEILRAMQRADEALSKDTAERLQLAVCDEPS EPEEEEETEVHEAYLSDKSEEDNYNESEEEAQPSVQGPRRSSRQVKKRRV ISDSESDIGGSDVEFKPDTKQEGSSDDASSGVGDSDSEDLGTFGKGAPKR KRAMVAQGGLRRKSLKKETGSAKRATPILSETKSTLSAFSAPQNSESQTH VSGGGNDSSGPTVWYHETLEWLKPEKRRDEHRRRPDHPEFNPTTLYVPEE FLNSCTPGMRKWWQLKSQNFDLVIFYKVGKFYELYHMDAVIGVSELGLIF MKGNWAHSGFPEIAFGRFSDSLVQKGYKVARVEQTETPEMMEARCRKMAH VSKFDRVVRREICRIITKGTQTYSVLDGDPSENYSRYLLSLKEKEEETSG HTRVYGVCFVDTSLGKFFIGQFSDDRHCSRFRTLVAHYPPVQILFEKGNL STETKTVLKGSLSSCLQEGLIPGSQFWDATKTLRTLLEGGYFTGNGDSST VLPLVLKGMTSESDSVGLTPGEESELALSALGGIVFYLKKCLIDQELLSM ANFEEYFPLDSDTVSTVKPGAVFTKASQRMVLDAVTLNNLEIFLNGTNGS TEGTLLERLDTCHTPFGKRLLKQWLCAPLCSPSAISDRLDAVEDLMAVPD KVTEVADLLKKLPDLERLLSKIHNVGSPLKSQNHPDSRAIMYEETTYSKK KIIDFLSALEGFKVMCKVSGLLEEVAGGFTSKTLKQVVTLQSKSPKGRFP DLTAELQRWDTAFDHEKARKTGLITPKAGFDSDYDQALADIRENEQSLLE YLDKQRSRLGCKSIVYWGIGRNRYQLEIPENFATRNLPEEYELKSTKKGC KRYWTKTIEKKLANLINAEERRDTSLKDCMRRLFCNFDKNHKDWQSAVEC IAVLDVLLCLANYSQGGDGPMCRPEIVLPGEDTHPFLEFKGSRHPCITKT FFGDDFIPNDILIGCEEEAEEHGKAYCVLVTGPNMGGKSTLIRQAGLLAV MAQLGCYVPAEKCRLTPVDRVFTRLGASDRIMSGESTFFVELSETASILR HATAHSLVLVDELGRGTATFDGTAIANAVVKELAETIKCRTLFSTHYHSL VEDYSKSVCVRLGHMACMVENECEDPSQETITFLYKFIKGACPKSYGFNA ARLANLPEEVIQKGHRKAREFERMNQSLQLFREVCLATEKPTINGEAIHR LLALINGL |
Msh6 (Mus musculus) belongs to following protein families:
References:
| Title | Authors | Journal |
| cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene. | Corradi A, Croci L, Stayton CL, Gulisano M, Boncinelli E, Consalez GG | Genomics Sept. 1, 1996 |
| Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. | Edelmann W, Yang K, Umar A, Heyer J, Lau K, Fan K, Liedtke W, Cohen PE, Kane MF, Lipford JR, Yu N, Crouse GF, Pollard JW, Kunkel T, Lipkin M, Kolodner R, Kucherlapati R | Cell Nov. 14, 1997 |
| Large-scale phosphorylation analysis of mouse liver. | Villen J, Beausoleil SA, Gerber SA, Gygi SP | Proc Natl Acad Sci U S A Feb. 1, 2007 |
Last modification of this entry: Oct. 6, 2010.
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