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{PDOC00574}
{PS00678; WD_REPEATS_1}
{PS50082; WD_REPEATS_2}
{PS50294; WD_REPEATS_REGION}
{BEGIN}
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* Trp-Asp (WD-40) repeats signature and profiles *
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Beta-transducin (G-beta) is one of the three subunits (alpha, beta, and gamma)
of  the  guanine   nucleotide-binding  proteins  (G proteins)   which  act  as
intermediaries  in  the  transduction  of  signals  generated by transmembrane
receptors [1]. The alpha subunit binds to and hydrolyzes GTP; the functions of
the beta and gamma subunits  are less clear but  they  seem to be required for
the  replacement  of  GDP  by  GTP as  well  as  for  membrane  anchoring  and
receptor recognition.

In higher eukaryotes G-beta  exists  as  a  small multigene family  of  highly
conserved  proteins  of  about  340  amino acid residues.  Structurally G-beta
consists of eight  tandem  repeats  of  about  40  residues, each containing a
central Trp-Asp  motif  (this  type  of  repeat  is  sometimes  called a WD-40
repeat). Such  a  repetitive  segment  has  been shown [2,3,4,5] to exist in a
number of other proteins listed below:

 - Yeast STE4, a component of the pheromone response pathway. STE4 is a G-beta
   like protein that associates with GPA1 (G-alpha) and STE18 (G-gamma).
 - Yeast MSI1, a negative  regulator  of RAS-mediated cAMP synthesis.  MSI1 is
   most probably also a G-beta protein.

 - Human and chicken protein 12.3.  The function of this protein is not known,
   but on the basis of its similarity to G-beta proteins, it may also function
   in signal transduction.
 - Chlamydomonas  reinhardtii  gblp. This protein is most probably the homolog
   of vertebrate protein 12.3.
 - Human LIS1, a neuronal protein involved in type-1 lissencephaly.
 - Mammalian  coatomer  beta'  subunit (beta'-COP), a component of a cytosolic
   protein complex  that  reversibly  associates  with Golgi membranes to form
   vesicles that mediate biosynthetic protein transport.

 - Yeast CDC4, essential for  initiation of DNA replication  and separation of
   the spindle pole bodies to form the poles of the mitotic spindle.
 - Yeast CDC20, a protein required  for  two  microtubule-dependent processes:
   nuclear movements prior to anaphase and chromosome separation.
 - Yeast MAK11, essential for  cell  growth  and  for  the  replication  of M1
   double-stranded RNA.
 - Yeast PRP4, a component of the U4/U6  small nuclear  ribonucleoprotein with
   a probable role in mRNA splicing.
 - Yeast PWP1, a protein of unknown function.
 - Yeast SKI8, a protein essential for controlling  the propagation of double-
   stranded RNA.
 - Yeast SOF1,  a  protein   required  for   ribosomal  RNA  processing  which
   associates with U3 small nucleolar RNA.
 - Yeast TUP1 (also known as AER2 or SFL2 or CYC9), a  protein  which has been
   implicated in    dTMP uptake,  catabolite repression, mating sterility, and
   many other phenotypes.
 - Yeast YCR57c, an ORF of unknown function from chromosome III.
 - Yeast YCR72c, an ORF of unknown function from chromosome III.

 - Slime mold coronin, an actin-binding protein.
 - Slime mold AAC3, a developmentally regulated protein of unknown function.

 - Drosophila protein Groucho (formerly known as E(spl); 'enhancer of split'),
   a protein  involved  in  neurogenesis  and  that seems to interact with the
   Notch and Delta proteins.
 - Drosophila TAF-II-80, a protein that is tightly associated with TFIID.

The number of repeats in the above  proteins varies between 5 (PRP4, TUP1, and
Groucho) and 8 (G-beta, STE4, MSI1, AAC3, CDC4, PWP1, etc.).  In G-beta and G-
beta like  proteins, the repeats span the entire length of the sequence, while
in other proteins,  they make up the N-terminal, the central or the C-terminal
section.

A signature pattern  can  be  developed  from  the  central core of the domain
(positions 9 to 23).

Two profiles were developed for this module, the first one picks up WD repeats
while  the  second  profile  is  'circular'  and  will  thus  detect  a region
containing adjacent WD repeats.

-Consensus pattern: [LIVMSTAC]-[LIVMFYWSTAGC]-[LIMSTAG]-[LIVMSTAGC]-x(2)-[DN]-
                    x-{P}-[LIVMWSTAC]-{DP}-[LIVMFSTAG]-W-[DEN]-[LIVMFSTAGCN]
-Sequences known to belong to this class detected by the pattern: A   majority.
 This pattern  does not detect ALL the occurrences of the domain in any of the
 above proteins, as some of the copies of the domain are less conserved.
-Other sequence(s) detected in Swiss-Prot: 95 other proteins,  but  in  all of
 them, the pattern is found only ONCE,  whereas it is generally found twice or
 more in WD-repeat proteins.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: 1.

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

-Last update: December 2004 / Pattern and text revised.

[ 1] Gilman A.G.
     "G proteins: transducers of receptor-generated signals."
     Annu. Rev. Biochem. 56:615-649(1987).
     PubMed=3113327; DOI=10.1146/annurev.bi.56.070187.003151
[ 2] Duronio R.J., Gordon J.I., Boguski M.S.
     "Comparative analysis of the beta transducin family with
     identification of several new members including PWP1, a nonessential
     gene of Saccharomyces cerevisiae that is divergently transcribed from
     NMT1."
     Proteins 13:41-56(1992).
     PubMed=1594577
[ 3] van der Voorn L., Ploegh H.L.
     FEBS Lett. 307:131-134(1992).
[ 4] Neer E.J., Schmidt C.J., Nambudripad R., Smith T.F.
     "The ancient regulatory-protein family of WD-repeat proteins."
     Nature 371:297-300(1994).
     PubMed=8090199; DOI=10.1038/371297b0
[ 5] Smith T.F., Gaitatzes C., Saxena K., Neer E.J.
     "The WD repeat: a common architecture for diverse functions."
     Trends Biochem. Sci. 24:181-185(1999).
     PubMed=10322433

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