InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Msh2

Summary

InnateDB Protein

IDBP-201485.6

Last Modified

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

Gene Symbol

Msh2

Protein Name

mutS homolog 2 (E. coli)

Synonyms

AI788990;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000024967

InnateDB Gene

IDBG-201483 (Msh2)

Protein Structure

UniProt Annotation

Function

Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis (By similarity). {ECO:0000250}.

Subcellular Localization

Nucleus {ECO:0000305}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 84 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	7 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	84 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0000400	four-way junction DNA binding
GO:0000403	Y-form DNA binding
GO:0000404	heteroduplex DNA loop binding
GO:0000406	double-strand/single-strand DNA junction binding
GO:0003677	DNA binding
GO:0003684	damaged DNA binding
GO:0003690	double-stranded DNA binding
GO:0003697	single-stranded DNA binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0008094	DNA-dependent ATPase activity
GO:0016887	ATPase activity
GO:0019237	centromeric DNA binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030983	mismatched DNA binding
GO:0032137	guanine/thymine mispair binding
GO:0032138	single base insertion or deletion binding
GO:0032139	dinucleotide insertion or deletion binding
GO:0032142	single guanine insertion binding
GO:0032143	single thymine insertion binding
GO:0032181	dinucleotide repeat insertion binding
GO:0032357	oxidized purine DNA binding
GO:0032405	MutLalpha complex binding
GO:0042803	protein homodimerization activity
GO:0043531	ADP binding

Biological Process

GO:0000710	meiotic mismatch repair
GO:0001701	in utero embryonic development
GO:0002204	somatic recombination of immunoglobulin genes involved in immune response
GO:0006119	oxidative phosphorylation
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006298	mismatch repair
GO:0006301	postreplication repair
GO:0006302	double-strand break repair
GO:0006311	meiotic gene conversion
GO:0006974	cellular response to DNA damage stimulus
GO:0007050	cell cycle arrest
GO:0007281	germ cell development
GO:0008340	determination of adult lifespan
GO:0008584	male gonad development
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010165	response to X-ray
GO:0010224	response to UV-B
GO:0016446	somatic hypermutation of immunoglobulin genes
GO:0016447	somatic recombination of immunoglobulin gene segments
GO:0019724	B cell mediated immunity
GO:0030183	B cell differentiation
GO:0031573	intra-S DNA damage checkpoint
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043524	negative regulation of neuron apoptotic process
GO:0043570	maintenance of DNA repeat elements
GO:0045128	negative regulation of reciprocal meiotic recombination
GO:0045190	isotype switching
GO:0045910	negative regulation of DNA recombination
GO:0051096	positive regulation of helicase activity

Cellular Component

GO:0000228	nuclear chromosome
GO:0005634	nucleus
GO:0016020	membrane
GO:0032301	MutSalpha complex
GO:0032302	MutSbeta complex

Protein Structure and Domains

PDB ID

MGI:101816

InterPro

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
IPR011184 DNA mismatch repair protein, MSH2
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00488
PF01624
PF05192
PF05188
PF05190

PRINTS

PIRSF

PIRSF005813

SMART

SM00534
SM00533

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt