{PDOC51805}
{PS51805; EPHD}
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* Extended PHD (ePHD) domain profile *
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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 alpha-helices separated by an
anti-parallel beta-sheet.  Three  cysteine  residues and one histidine residue
from the  N-terminal  loop, beta2-strand, and alpha2-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 beta-sheet and one long anti-parallel
beta-sheet that are linked by one alpha 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2016 / First entry.

[ 1] Liu L., Qin S., Zhang J., Ji P., Shi Y., Wu J.
     "Solution structure of an atypical PHD finger in BRPF2 and its
     interaction with DNA."
     J. Struct. Biol. 180:165-173(2012).
     PubMed=22820306; DOI=10.1016/j.jsb.2012.06.014
[ 2] Liu Z., Li F., Ruan K., Zhang J., Mei Y., Wu J., Shi Y.
     "Structural and functional insights into the human
     Borjeson-Forssman-Lehmann syndrome-associated protein PHF6."
     J. Biol. Chem. 289:10069-10083(2014).
     PubMed=24554700; DOI=10.1074/jbc.M113.535351
[ 3] Chen S., Yang Z., Wilkinson A.W., Deshpande A.J., Sidoli S.,
     Krajewski K., Strahl B.D., Garcia B.A., Armstrong S.A., Patel D.J.,
     Gozani O.
     "The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate
     DOT1L-Mediated Methylation of H3K79."
     Mol. Cell 60:319-327(2015).
     PubMed=26439302; DOI=10.1016/j.molcel.2015.08.019
[ 4] Klein B.J., Muthurajan U.M., Lalonde M.-E., Gibson M.D., Andrews F.H.,
     Hepler M., Machida S., Yan K., Kurumizaka H., Poirier M.G., Cote J.,
     Luger K., Kutateladze T.G.
     "Bivalent interaction of the PZP domain of BRPF1 with the nucleosome
     impacts chromatin dynamics and acetylation."
     Nucleic Acids Res. 44:472-484(2016).
     PubMed=26626149; DOI=10.1093/nar/gkv1321

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