{PDOC50302}
{PS50302; PUM}
{PS50303; PUM_HD}
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* Pumilio RNA-binding repeat and homology domain profiles *
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Members  of the Pumilio family of proteins (Puf) regulate translation and mRNA
stability  in a wide variety of eukaryotic organisms including mammals, flies,
worms,  slime mold, and yeast [1]. Pumilio family members are characterized by
the  presence of eight tandem copies of an imperfectly repeated 36 amino acids
sequence  motif,  the  Pumilio repeat, surrounded by a short N- and C-terminal
conserved region. The eight repeats and the N- and C-terminal regions form the
Pumilio homology domain (PUM-HD). The PUM-HD domain is a sequence-specific RNA
binding  domain.  Several  Puf  members  have  been shown to bind specific RNA
sequences  mainly  found  in  the 3' UTR of mRNA and repress their translation
[2].  Frequently,  Puf  proteins  function  asymmetrically  to  create protein
gradients,  thus  causing  asymmetric  cell  division and regulating cell fate
specification [3].

Crystal structure of Pumilio repeats has been solved (see <PDB:1IB2>) [4]. The
PUM  repeat  with  the  N-  and  C-terminal  regions  pack  together to form a
right-handed superhelix that approximates a half doughnut structurally similar
to  the  Armadillo  (ARM)  repeat proteins (see <PDOC50176>), beta-catenin and
karyopherin  alpha.  The  RNA binds the concave surface of the molecule, where
each  of  the protein's eight repeats makes contacts with a different RNA base
via three amino acid side chains at conserved positions [5].

Some of the proteins known to contain Pumilio repeats are listed below:

 - Drosophila  Pumilio  protein. It is a sequence-specific RNA-binding protein
   that  binds  to  the  Nanos Response Element (NRE), a 16 bp sequence in the
   hunchback mRNA 3'UTR.
 - Xenopus Pumilio. It also interacts with a Nanos protein, Xcat-2.
 - Human  PUM1 and PUM2. They have an important role in cell development, fate
   specification and differentiation.
 - Yeast   PUF3  protein.  It  is  a  transcript-specific  regulator  of  mRNA
   degradation and binds the 3'UTR of the COX17 protein.
 - Dictyostelium  PufA  protein.  It  represses expression of protein kinase A
   mRNA, and appears to be a key developmental regulator in that organism.
 - Caenorhabditis  elegans  fbf-1  and  fbf-2.  They  mediate the sperm/oocyte
   switch in  hermaphrodites  by  binding  the  3'  UTR  of the fem-3 mRNA and
   repressing its expression.

Two  profiles were developed for this conserved region, the first one picks up
pumilio repeat units while the second one detects the whole PUM-HD domain.

-Sequences known to belong to this class detected by the profile: ALL pumillio
 repeats.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL   PUM-HD
 domains.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: January 2004 / First entry.

[ 1] Parisi M., Lin H.
     "Translational repression: a duet of Nanos and Pumilio."
     Curr. Biol. 10:R81-R83(2000).
     PubMed=10662662
[ 2] Spassov D.S., Jurecic R.
     "The PUF family of RNA-binding proteins: does evolutionarily conserved
     structure equal conserved function?"
     IUBMB Life 55:359-366(2003).
     PubMed=14584586
[ 3] Barker D.D., Wang C., Moore J., Dickinson L.K., Lehmann R.
     "Pumilio is essential for function but not for distribution of the
     Drosophila abdominal determinant Nanos."
     Genes Dev. 6:2312-2326(1992).
     PubMed=1459455
[ 4] Wang X., Zamore P.D., Hall T.M.
     "Crystal structure of a Pumilio homology domain."
     Mol. Cell 7:855-865(2001).
     PubMed=11336708
[ 5] Wang X., McLachlan J., Zamore P.D., Hall T.M.
     "Modular recognition of RNA by a human pumilio-homology domain."
     Cell 110:501-512(2002).
     PubMed=12202039

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