CPLM-011126

Genbank Nucleotide ID

DNA mismatch repair protein MSH6

Protein Synonyms/Alias

MutS protein homolog 6; Postmeiotic segregation protein 3

PMS3; YDR097C; YD8557.04C

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Position	Peptide	Type	References
36	SLLSFFSKQVPSGTP	acetylation	[1]
848	WVQMAANKTYKRYYS	acetylation	[1]

[1] Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae.
Henriksen P, Wagner SA, Weinert BT, Sharma S, Bacinskaja G, Rehman M, Juffer AH, Walther TC, Lisby M, Choudhary C.
Mol Cell Proteomics. 2012 Nov;11(11):1510-22. [PMID: 22865919]

Functional Description

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. MSH6 provides substrate-binding and substrate-specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. Acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. 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 by the MutS alpha complex is crucial for MMR. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. May also be involved in resolution of recombination intermediates.

DNA_BIND 228 299
NP_BIND 982 989 ATP (Potential).
REGION 305 421 Mispair-binding domain.
MOTIF 27 34 PIP box.
MOD_RES 102 102 Phosphoserine; by ATM or ATR.
MOD_RES 130 130 Phosphoserine; by ATM or ATR.
MOD_RES 145 145 Phosphoserine.
MOD_RES 150 150 Phosphoserine.
MOD_RES 201 201 Phosphoserine.
MOD_RES 451 451 Phosphothreonine.

ATP-binding; Complete proteome; DNA damage; DNA repair; DNA-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:SGD.
GO:0032301; C:MutSalpha complex; IPI:SGD.
GO:0000228; C:nuclear chromosome; IBA:RefGenome.
GO:0005524; F:ATP binding; IDA:SGD.
GO:0003684; F:damaged DNA binding; IBA:RefGenome.
GO:0008094; F:DNA-dependent ATPase activity; IBA:RefGenome.
GO:0000400; F:four-way junction DNA binding; IDA:SGD.
GO:0030983; F:mismatched DNA binding; IEA:InterPro.
GO:0036297; P:interstrand cross-link repair; IGI:SGD.
GO:0043570; P:maintenance of DNA repeat elements; IBA:RefGenome.
GO:0000710; P:meiotic mismatch repair; IMP:SGD.
GO:0045910; P:negative regulation of DNA recombination; IBA:RefGenome.
GO:0007131; P:reciprocal meiotic recombination; IBA:RefGenome.
GO:0009411; P:response to UV; IBA:RefGenome.

IPR017261; DNA_mismatch_repair_Msh6.
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.

PF01624; MutS_I
PF05188; MutS_II
PF05192; MutS_III
PF05190; MutS_IV
PF00488; MutS_V

SM00534; MUTSac
SM00533; MUTSd

PS00486; DNA_MISMATCH_REPAIR_2