PROSITE documentation PDOC51058
Zinc finger CXXC-type profile


Methylation of cytosine within the dinucleotide CpG is essential for vertebrate development and is correlated to gene silencing. Sequence analyses on various mammalian proteins linked to DNA methylation led to the identification of a conserved cysteine rich region with the consensus sequence C-x(2)-C-x(2)-C-x(5)-C-x(2)-C-x(2)-C, the CXXC-type zinc finger [1,2]. This zinc finger can bind specifically to non-methylated CpG DNA but failed to bind to methylated CpG motifs [3,4].

Some proteins known to contain a CXXC-type zinc finger are listed below:

  • Mammalian DNA (cytosine-5)-methyltransferase protein 1.
  • Methyl-CpG binding domain protein 1 (MBD1).
  • Human Mixed Lineage Leukemia (MLL) protein (also known as all1, htrx, trx1, or hrx). The MLL gene is a frequent target for chromosomal aberration associated with leukemia. In the majority of leukemias with altered MLL the complete C-terminus is removed by chromosomal translocation and replaced in frame by a variety of different fusion partners. The N-terminal CXXC-type zinc finger of MLL is essential for the oncongenic activity of various MLL fusion proteins [4,5].
  • Human CpG binding protein hCGBP, an activator of genes residing within CpG islands.

The profile we developed covers the whole CXXC-type zinc finger.

Last update:

January 2005 / First entry.


Technical section

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

ZF_CXXC, PS51058; Zinc finger CXXC-type profile  (MATRIX)


1AuthorsMa Q. Alder H. Nelson K.K. Chatterjee D. Gu Y. Nakamura T. Canaani E. Croce C.M. Siracusa L.D. Buchberg A.M.
TitleAnalysis of the murine All-1 gene reveals conserved domains with human ALL-1 and identifies a motif shared with DNA methyltransferases.
SourceProc. Natl. Acad. Sci. U.S.A. 90:6350-6354(1993).
PubMed ID8327517

2AuthorsCross S.H. Meehan R.R. Nan X. Bird A.
TitleA component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins.
SourceNat. Genet. 16:256-259(1997).
PubMed ID9207790

3AuthorsVoo K.S. Carlone D.L. Jacobsen B.M. Flodin A. Skalnik D.G.
TitleCloning of a mammalian transcriptional activator that binds unmethylated CpG motifs and shares a CXXC domain with DNA methyltransferase, human trithorax, and methyl-CpG binding domain protein 1.
SourceMol. Cell. Biol. 20:2108-2121(2000).
PubMed ID10688657

4AuthorsBirke M. Schreiner S. Garcia-Cuellar M.P. Mahr K. Titgemeyer F. Slany R.K.
TitleThe MT domain of the proto-oncoprotein MLL binds to CpG-containing DNA and discriminates against methylation.
SourceNucleic Acids Res. 30:958-965(2002).
PubMed ID11842107

5AuthorsAyton P.M. Chen E.H. Cleary M.L.
TitleBinding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein.
SourceMol. Cell. Biol. 24:10470-10478(2004).
PubMed ID15542854

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