PROSITE documentation PDOC50016

{PDOC50016}
{PS01359; ZF_PHD_1}
{PS50016; ZF_PHD_2}
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* Zinc finger PHD-type signature and profile *
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The  Plant   Homeodomain  (PHD)  type  zinc  finger    (C4HC3) [1] is found in
nuclear  proteins thought to be involved in chromatin-mediated transcriptional
regulation.  The  PHD  finger  motif  is reminiscent of, but distinct from the
C3HC4-type RING finger. A general function of the PHD finger is not yet known,
but in  the CREB-binding protein (CBP) it is an integral part of the enzymatic
core of  the  acetyltransferase    domain and is also a key contributor to the
transcriptional activity of CBP.

The 3D   structure  of  Williams-Beuren  Syndrome  transcription  factor  (see
<PDB:1F62>) reveals  that  the  PHD  finger coordinates two atoms of zinc in a
cross-braced manner [2]. This atypical conformation is also shared by the FYVE
(see <PDOC50178>  and  RING  fingers (see <PDOC00449>). The two zinc sites are
located at opposite ends of a short beta-sheet. This feature is also shared by
the RING  finger  and  the  FYVE  domain,  but  the  structure  differ  in the
surrounding loops  that  vary  significantly  in length and sequence and could
explain the wide variety of functions between these three domains.

Single or multiple PHD fingers are found in the following proteins:

 - Drosophila trithorax protein and the homologous mammalian protein HRX (also
   known  as  ALL1,  MLL and  Htrx). The trithorax gene is required for proper
   regulation of  the homeotic genes in flies [3]. The HRX gene is involved in
   translocations  in  acute  lymphoblastic  leukemia.  Trithorax  has  4  PHD
   fingers. The most C-terminal one in HRX is degenerated.
 - Drosophila   Polycomblike,  a  protein  encoded  by a Polycomb-group  gene.
   Polycomblike  and the   Polycomb-group   genes  are  required  for  correct
   regulation  of the homeotic  genes  in flies.  These genes  counteract  the
   effects  of the  trithorax-group  genes  presumably by creating an inactive
   chromatin structure [4]. Polycomblike has 2 PHD fingers.
 - Human Xe169 and murine Smcx, proteins encoded by X-linked genes that escape
   X-chromosome  inactivation.  Murine Smcy is a related gene on the Y chromo-
   some. Xe169 has 2 PHD fingers.
 - Human RBP2, a Xe169-related protein thought to bind to the Rb protein.
 - Human  Br140  (also  known  as  peregrin),  a  protein  which  also  has  a
   bromodomain.
 - Medicago sativa Alfin-1, a presumptive transcription factor.
 - A  group  of  plant homeobox-containg proteins such as Arabidopsis HAT3 and
   PRHA, maize ZMHOX1a, parsley PRHP.
 - Human Mi-2 autoantigen.
 - Drosophila shuttle craft protein.
 - Human BS69, a protein that binds adenovirus E1A.
 - Murine CBP  (CREB-binding protein),  the  closely related human E1A binding
   protein p300, and YNJ1, a related protein from C.elegans
 - Mammalian zinc-finger protein of the 'requiem' family.
 - Human TIF1, a putative transcriptional mediator for nuclear receptors.

The consensus  pattern we developed start at the first cysteine and end at the
last one, whereas the profile we developed spans the complete domain.

-Consensus pattern: C-x(1,2)-C-x(5,45)-[VMFLWIE]-x-C-x(1,4)-C-x(1,4)-
                    [WYFVQHLT]-H-x(2)-C-x(5,45)-[WFLYI]-x-C-x(2)-C
-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL,  except
 for shuttle craft protein.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: The  spacing between  cysteines in the PHD finger is closely related to
 that in the RING finger. Discrimination between these two domains with either
 a  pattern  or a  profile  is  therefore difficult, and some rare domains are
 recognized by both the RING and PHD descriptors.

-Expert(s) to contact by email:
           Aasland R.; 





aasland@mbi.uib.no


-Last update: May 2002 / First entry.

[ 1] Aasland R., Gibson T.J., Stewart A.F.
     "The PHD finger: implications for chromatin-mediated transcriptional
     regulation."
     Trends Biochem. Sci. 20:56-59(1995).
     PubMed=7701562
[ 2] Pascual J., Martinez-Yamout M., Dyson H.J., Wright P.E.
     "Structure of the PHD zinc finger from human Williams-Beuren syndrome
     transcription factor."
     J. Mol. Biol. 304:723-729(2000).
     PubMed=11124022; DOI=10.1006/jmbi.2000.4308
[ 3] Kennison J.A.
     "Transcriptional activation of Drosophila homeotic genes from distant
     regulatory elements."
     Trends Genet. 9:75-79(1993).
     PubMed=8098166
[ 4] Paro R.
     "Mechanisms of heritable gene repression during development of
     Drosophila."
     Curr. Opin. Cell Biol. 5:999-1005(1993).
     PubMed=7907493

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