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PROSITE documentation PDOC00089

C-5 cytosine-specific DNA methylases signatures


C-5 cytosine-specific DNA methylases (EC (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA [1,2,3]. Such enzymes are found in the proteins described below.

  • As a component of type II restriction-modification systems in prokaryotes and some bacteriophages. Such enzymes recognize a specific DNA sequence where they methylate a cytosine. In doing so, they protect DNA from cleavage by type II restriction enzymes that recognize the same sequence. The sequences of a large number of type II C-5 Mtases are known.
  • In vertebrates, there are a number of C-5 Mtases that methylate CpG dinucleotides. The sequence of the mammalian enzyme is known.

C-5 Mtases share a number of short conserved regions. We selected two of them. The first is centered around a conserved Pro-Cys dipeptide in which the cysteine has been shown [4] to be involved in the catalytic mechanism; it appears to form a covalent intermediate with the C6 position of cytosine. The second region is located at the C-terminal extremity in type-II enzymes.


In the first position of the second pattern, most known Mtases have Arg or Lys.

Expert(s) to contact by email:

Roberts R.J.
Bickle T.
Mugasimangalam R.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

C5_MTASE_1, PS00094; C-5 cytosine-specific DNA methylases active site  (PATTERN)

C5_MTASE_2, PS00095; C-5 cytosine-specific DNA methylases C-terminal signature  (PATTERN)


1AuthorsPosfai J., Bhagwat A.S., Roberts R.J.
TitleSequence motifs specific for cytosine methyltransferases.
SourceGene 74:261-265(1988).
PubMed ID3248729

2AuthorsKumar S., Cheng X., Klimasauskas S., Mi S., Posfai J., Roberts R.J., Wilson G.G.
TitleThe DNA (cytosine-5) methyltransferases.
SourceNucleic Acids Res. 22:1-10(1994).
PubMed ID8127644

3AuthorsLauster R., Trautner T.A., Noyer-Weidner M.
TitleCytosine-specific type II DNA methyltransferases. A conserved enzyme core with variable target-recognizing domains.
SourceJ. Mol. Biol. 206:305-312(1989).
PubMed ID2716049

4AuthorsChen L., MacMillan A.M., Chang W., Ezaz-Nikpay K., Lane W.S., Verdine G.L.
TitleDirect identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase.
SourceBiochemistry 30:11018-11025(1991).
PubMed ID1932026

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