The extended plant homeodomain (ePHD) domain contains an N-terminal pre-PHD (C2HC zinc finger), a long linker, and a noncanonical PHD finger (C4HC3 zinc finger) (see <PDOC50016>). The ePHD domain can bind dsDNA but not histones [1,2,3,4].

The pre-PHD-type C2HC zinc finger and the PHD finger in the ePHD domain are associated with each other via extensive hydrophobic interactions and numerous hydrogen bonding interactions and folded as an intact structural module. The pre-PHD-type C2HC zinc finger consists of two α-helices separated by an anti-parallel β-sheet. Three cysteine residues and one histidine residue from the N-terminal loop, β2-strand, and α2-helix coordinate one zinc ion (designated Zn1). The C-terminal part of the ePHD domain is a PHD finger, consisting of one short anti-parallel β-sheet and one long anti-parallel β-sheet that are linked by one α helix (see <PDB:4NN2>). Like other PHD fingers, the PHD finger of the ePHD domain consists of two interleaved zinc fingers. A pair of bound zinc ions (designated Zn2 and Zn3) specifically stabilizes the characteristic cross-braced folding topology of the PHD finger. Each zinc ion is coordinated by a combination of four cysteine and histidine residues in which the Zn3 ion is coordinated by a C3H motif instead of a C4 motif [1,2].

Some proteins known to contain a ePHD domain are listed below:

• Vertebrate plant homeodomain finger 6 (PHF6), a multidomain protein that comprises four nuclear localization signals and two ePHD domains. It is implicated in chromatin regulation and neural development.
• Vertebrate MLL1/2/3/4, histone methyltransferases.
• Vertebrate JMJD2A/B/C, histone demethylases.
• Vertebrate Bromodomain- and PHD finger-containing protein 1, 2, and 3 (BRPF1/2/3), a component of MOZ (monocytic leukemia zinc finger)/MORF (MOZ- related factor) histone acetyltransferase complex.
• Vertebrate JADE1/2/3, components of the HBO1 complex which has a histone H4-specific acetyltransferase activity.
• AF10/17, subunits of the multimeric DOT1L complex that mediates H3K79 methylation.
• Caenorhabditis elegans protein lin-49, a component of a histone modifying complex.
• Yeast NuA3 HAT complex component NTO1.

The profile we developed covers both the pre-PHD-type C2HC zinc finger and the PHD finger of the ePHD domain.