DNA mismatch repair MutH/Restriction endonuclease, type II (IPR011337)

Short name: DNA_rep_MutH/RE_typeII

Overlapping homologous superfamilies

Domain relationships



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 [PMID: 15121719, PMID: 12665693], as summarised below:

  • Type I enzymes (EC: 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: activities.
  • Type II enzymes (EC: cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.
  • Type III enzymes (EC: 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:
  • Type IV enzymes target methylated DNA.

Type II restriction endonucleases (EC: 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 beta-strands and one alpha-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin [PMID: 15770420]. However, there is still considerable diversity amongst restriction endonucleases [PMID: 14576294, PMID: 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 [PMID: 11557805].

This entry represents restriction endonucleases EcoRV, NaeI, HincII, and Sau3AI, as well as the DNA mismatch repair protein MutH, which are closely related in sequence and structure. EcoRV recognises the DNA sequence GATATC and cleaves after T-1 [PMID: 15170321], NaeI recognises GCCGCC and cleaves after C-2 [PMID: 10856254], HincII recognises GTYRAC and cleaves after the pyrimidine Y [PMID: 15476804], and Sau3AI recognises GATC and cleaves prior to G-1 [PMID: 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 [PMID: 9482749].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0003677 DNA binding
GO:0004519 endonuclease activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.