MutH DNA mismatch repair enzyme MutH
SMART ACC:	SM000927
Description:	MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL (PUBMED:9482749).
InterPro ACC:	IPR011337
InterPro abstract:	There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements [ PUBMED:15121719 … expand There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements [ PUBMED:15121719 PUBMED:12665693 ], as summarised below: Type I enzymes ( EC:3.1.21.3 ) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase ( EC:2.1.1.72 ) activities. Type II enzymes ( EC:3.1.21.4 ) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase. Type III enzymes ( EC:3.1.21.5 ) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase ( EC:2.1.1.72 ). Type IV enzymes target methylated DNA. Type II restriction endonucleases ( EC:3.1.21.4 ) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin [ PUBMED:15770420 ]. However, there is still considerable diversity amongst restriction endonucleases [ PUBMED:14576294 PUBMED:11827971 ]. The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone [ PUBMED:11557805 ]. This entry includes the restriction endonuclease Sau3AI and the DNA mismatch repair protein MutH, which are closely related in sequence and structure. Sau3AI recognises GATC and cleaves prior to G-1 [ PUBMED:11316811 ]. MutH, along with MutS and MutL, is essential for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL. With sequence homology to Sau3AI and structural similarity to PvuII endonuclease, MutH shows sequence and structural similarity with PvuII and Sau3AI, indicating a strong relationship with these enzymes through divergent evolution, suggesting that type II restriction endonucleases evolved from a common ancestor [ PUBMED:9482749 ]. collapse
GO function:	endonuclease activity (GO:0004519), DNA binding (GO:0003677)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 1 748 MutH domains in 1 747 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing MutH domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MutH domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Predicted cellular role

Cellular role:	Transport

Relevant references for this domain

Primary literature for the MutH domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a MutH domain which could be assigned to a KEGG orthologous group, and not all proteins containing MutH domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

KEGG orthologous groups

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR011337
Pfam	MutH