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C-5 cytosine-specific DNA methylases (EC 2.1.1.37) (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.

Roberts R.J.
Bickle T.
Mugasimangalam R.

December 2004 / Pattern and text revised.

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

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

Consensus pattern: [DENKS]-x-[FLIV]-x(2)-[GSTC]-x-P-C-x-{V}-[FYWLIM]-S C is the active site residue Sequences known to belong to this class detected by the pattern: ALL, except for M.MthtI Other sequence(s) detected in Swiss-Prot: 3.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00094 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00094 • Scan Swiss-Prot/TrEMBL entries against PS00094 • view ligand binding statistics

Matching PDB structures: 10MH 1DCT 1FJX 1HMY ... [ALL]

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

Consensus pattern: [RKQGTF]-x(2)-G-N-[SA]-[LIVF]-x-[VIP]-x-[LVMT]-x(3)-[LIVM]-x(3)-[LIVM] Sequences known to belong to this class detected by the pattern: ALL, except for M.AluI, M.HgaI 1 and 2, and M.HpaII Other sequence(s) detected in Swiss-Prot: 2.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00095 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00095 • Scan Swiss-Prot/TrEMBL entries against PS00095 • view ligand binding statistics

Matching PDB structures: 10MH 1DCT 1FJX 1G55 ... [ALL]

1	Authors	Posfai J., Bhagwat A.S., Roberts R.J.
	Title	Sequence motifs specific for cytosine methyltransferases.
	Source	Gene 74:261-265(1988).
	PubMed ID	3248729

2	Authors	Kumar S., Cheng X., Klimasauskas S., Mi S., Posfai J., Roberts R.J., Wilson G.G.
	Title	The DNA (cytosine-5) methyltransferases.
	Source	Nucleic Acids Res. 22:1-10(1994).
	PubMed ID	8127644

3	Authors	Lauster R., Trautner T.A., Noyer-Weidner M.
	Title	Cytosine-specific type II DNA methyltransferases. A conserved enzyme core with variable target-recognizing domains.
	Source	J. Mol. Biol. 206:305-312(1989).
	PubMed ID	2716049

4	Authors	Chen L., MacMillan A.M., Chang W., Ezaz-Nikpay K., Lane W.S., Verdine G.L.
	Title	Direct identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase.
	Source	Biochemistry 30:11018-11025(1991).
	PubMed ID	1932026

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