InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mlh1

Summary

InnateDB Protein

IDBP-202757.6

Last Modified

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

Gene Symbol

Mlh1

Protein Name

mutL homolog 1 (E. coli)

Synonyms

1110035C23Rik; AI317206; AI325952; AI561766;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000035079

InnateDB Gene

IDBG-202755 (Mlh1)

Protein Structure

UniProt Annotation

Function

Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS- heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis (By similarity). {ECO:0000250}.

Subcellular Localization

Nucleus {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 135 interaction(s) predicted by orthology.

Predicted by orthology
Total	135 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003697	single-stranded DNA binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016887	ATPase activity
GO:0030983	mismatched DNA binding
GO:0032137	guanine/thymine mispair binding
GO:0032407	MutSalpha complex binding
GO:0043566	structure-specific DNA binding

Biological Process

GO:0000289	nuclear-transcribed mRNA poly(A) tail shortening
GO:0000712	resolution of meiotic recombination intermediates
GO:0002204	somatic recombination of immunoglobulin genes involved in immune response
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006298	mismatch repair
GO:0006303	double-strand break repair via nonhomologous end joining
GO:0006974	cellular response to DNA damage stimulus
GO:0007060	male meiosis chromosome segregation
GO:0007126	meiotic nuclear division
GO:0007129	synapsis
GO:0007131	reciprocal meiotic recombination
GO:0007140	male meiosis
GO:0007283	spermatogenesis
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0016446	somatic hypermutation of immunoglobulin genes
GO:0016447	somatic recombination of immunoglobulin gene segments
GO:0043060	meiotic metaphase I plate congression
GO:0045132	meiotic chromosome segregation
GO:0045190	isotype switching
GO:0045950	negative regulation of mitotic recombination
GO:0048477	oogenesis
GO:0051257	spindle midzone assembly involved in meiosis

Cellular Component

GO:0000793	condensed chromosome
GO:0000794	condensed nuclear chromosome
GO:0000795	synaptonemal complex
GO:0001673	male germ cell nucleus
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005694	chromosome
GO:0005712	chiasma
GO:0016020	membrane
GO:0032389	MutLalpha complex

Protein Structure and Domains

PDB ID

MGI:101938

InterPro

IPR002099 DNA mismatch repair protein family
IPR003594 Histidine kinase-like ATPase, ATP-binding domain
IPR013507 DNA mismatch repair protein, C-terminal
IPR020568 Ribosomal protein S5 domain 2-type fold

PFAM

PF02518
PF13581
PF01119

PRINTS

PIRSF

SMART

SM00387

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9JK91