{PDOC51818}
{PS51818; HOMEO_PROSPERO}
{BEGIN}
***************************************
* Homeo-Prospero (HPD) domain profile *
***************************************

The prospero-related   homeoproteins   Prox1  and  Prox2  are  the  vertebrate
homologs of   the   Drosophila   melanogaster  homeodomain-containing  protein
Prospero, the  founder  member of a family of transcription factors which have
been shown  to  play  critical  roles  in  many developmental events. The only
common feature of this family of proteins is the 160-residue C-terminal Homeo-
Prospero domain  (HPD),  which consists of a highly divergent homeodomain (HD)
and an  associated  Prospero  domain  (PD)  that  are  essential for sequence-
specific DNA  binding and the transcriptional activation function of Prospero.
The structure of these two regions consists of a single structural unit (HPD),
in which  the  Prospero  domain  region  is  in  position to contribute to DNA
binding and  also  to  mask a defined nuclear export signal that is within the
homeodomain region.  The  HPD  domain  coordinately regulates Prospero nuclear
localization and  DNA  binding  specificity.  The  HPD  domain is required for
nearly all  the  known functions of Prospero, including regulation of nuclear/
cytoplasmic localization,  sequence-specific  DNA binding, and transcriptional
activation [1,2,3,4,5,6].

The HD  region  does  assume  an overall fold very similar to homeodomains but
with one  striking difference. In the homeodomain structure, the so-called DNA
recognition helix  is either at the extreme C-terminus of the protein or leads
into a flexible linker of variable length that connects to another essentially
independent domain.  In the HPD domain the recognition helix (alpha3) connects
the HD  region and the PD region as a single structural unit (see <PDB:1MIJ>).
The PD  region can be described as a four-helix bundle (alpha3-alpha6). At the
extreme C  terminus of the HPD domain, a short helix is masked by the PD. When
this helix is unmasked, Prospero is exported from the nucleus [2,3].

The profile we developed covers the entire HPD domain.

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

[ 1] Tomarev S.I., Sundin O., Banerjee-Basu S., Duncan M.K., Yang J.-M.,
     Piatigorsky J.
     "Chicken homeobox gene Prox 1 related to Drosophila prospero is
     expressed in the developing lens and retina."
     Dev. Dyn. 206:354-367(1996).
     PubMed=8853985; DOI=10.1002/(SICI)1097-0177(199608)206:4<354::AID-AJA2>3.0.CO;2-H
[ 2] Ryter J.M., Doe C.Q., Matthews B.W.
     "Structure of the DNA binding region of prospero reveals a novel
     homeo-prospero domain."
     Structure 10:1541-1549(2002).
     PubMed=12429095
[ 3] Yousef M.S., Matthews B.W.
     "Structural basis of Prospero-DNA interaction: implications for
     transcription regulation in developing cells."
     Structure 13:601-607(2005).
     PubMed=15837198; DOI=10.1016/j.str.2005.01.023
[ 4] Chen X., Patel T.P., Simirskii V.I., Duncan M.K.
     "PCNA interacts with Prox1 and represses its transcriptional
     activity."
     Mol. Vis. 14:2076-2086(2008).
     PubMed=19023449
[ 5] Nishijima I., Ohtoshi A.
     "Characterization of a novel prospero-related homeobox gene, Prox2."
     Mol. Genet. Genomics 275:471-478(2006).
     PubMed=16470382; DOI=10.1007/s00438-006-0105-0
[ 6] Pistocchi A., Bartesaghi S., Cotelli F., Del Giacco L.
     "Identification and expression pattern of zebrafish prox2 during
     embryonic development."
     Dev. Dyn. 237:3916-3920(2008).
     PubMed=19035352; DOI=10.1002/dvdy.21798

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}