InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Msh6

Summary

InnateDB Protein

IDBP-201550.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Msh6

Protein Name

mutS homolog 6 (E. coli)

Synonyms

AU044881; AW550279; GTBP; Gtmbp;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000005503

InnateDB Gene

IDBG-201548 (Msh6)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

Nucleus {ECO:0000250}. Chromosome {ECO:0000250}. Note=Associates with H3K36me3 via its PWWP domain. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 51 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	8 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	51 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0000400	four-way junction DNA binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003684	damaged DNA binding
GO:0003690	double-stranded DNA binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008094	DNA-dependent ATPase activity
GO:0016887	ATPase activity
GO:0030983	mismatched DNA binding
GO:0032137	guanine/thymine mispair binding
GO:0032138	single base insertion or deletion binding
GO:0032142	single guanine insertion binding
GO:0032143	single thymine insertion binding
GO:0032357	oxidized purine DNA binding
GO:0032405	MutLalpha complex binding
GO:0035064	methylated histone binding
GO:0043531	ADP binding

Biological Process

GO:0000710	meiotic mismatch repair
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006298	mismatch repair
GO:0007131	reciprocal meiotic recombination
GO:0008340	determination of adult lifespan
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009411	response to UV
GO:0016446	somatic hypermutation of immunoglobulin genes
GO:0016447	somatic recombination of immunoglobulin gene segments
GO:0043570	maintenance of DNA repeat elements
GO:0045190	isotype switching
GO:0045910	negative regulation of DNA recombination
GO:0051096	positive regulation of helicase activity
GO:0097193	intrinsic apoptotic signaling pathway

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0032301	MutSalpha complex
GO:0043231	intracellular membrane-bounded organelle

Protein Structure and Domains

PDB ID

MGI:1343961

InterPro

IPR000313 PWWP domain
IPR000432 DNA mismatch repair protein MutS, C-terminal
IPR007695 DNA mismatch repair protein MutS-like, N-terminal
IPR007696 DNA mismatch repair protein MutS, core
IPR007860 DNA mismatch repair protein MutS, connector domain
IPR007861 DNA mismatch repair protein MutS, clamp
IPR016151 DNA mismatch repair protein MutS, N-terminal
IPR017261 DNA mismatch repair protein Msh6
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00855
PF00488
PF01624
PF05192
PF05188
PF05190

PRINTS

PIRSF

PIRSF037677

SMART

SM00293
SM00534
SM00533

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt