{PDOC50309}
{PS50309; DC}
{BEGIN}
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* Doublecortin domain profile *
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X-linked lissencephaly   is  a  severe  brain  malformation  affecting  males.
Recently it  has been demonstrated that the doublecortin gene is implicated in
this disorder   [1].  Doublecortin  was  found  to  bind  to  the  microtubule
cytoskeleton. In  vivo  and  in vitro assays show that Doublecortin stabilizes
microtubules and  causes bundling [2]. Doublecortin is a basic protein with an
iso-electric point  of  10,  typical of microtubule-binding proteins. However,
its sequence contains no known microtubule-binding domain(s).

The detailed  sequence analysis of Doublecortin and Doublecortin-like proteins
allowed the  identification  of  an evolutionarily conserved Doublecortin (DC)
domain. This domain is found in the N-terminus of proteins and consists of one
or two tandemly repeated copies of an around 80 amino acids region [3]. It has
been suggested  that  the  first DC domain of Doublecortin  binds  tubulin and
enhances microtubule polymerization [3].

Some proteins known to contain a DC domain are listed below:

 - Doublecortin.  It is required for neuronal migration [1]. A large number of
   point mutations  in the human DCX gene leading to lissencephaly are located
   within the DC domains [3].
 - Human serine/threonine-protein kinase DCAMKL1. It is a probable kinase that
   may be   involved   in  a  calcium-signaling  pathway  controling  neuronal
   migration in the developing brain [4].
 - Retinitis pigmentosa 1 protein. It could play a role in the differentiation
   of photoreceptor  cells.  Mutation  in  the  human RP1 gene cause retinitis
   pigmentosa of type 1 [5].

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2001 / First entry.

[ 1] Des Portes V., Pinard J.M., Billuart P., Vinet M.C., Koulakoff A.,
     Carrie A., Gelot A., Dupuis E., Motte J., Berwald-Netter Y.,
     Catala M., Kahn A., Beldjord C., Chelly J.
     Cell 92:51-61(1998).
[ 2] Horesh D., Sapir T., Francis F., Wolf S.G., Caspi M., Elbaum M.,
     Chelly J., Reiner O.
     "Doublecortin, a stabilizer of microtubules."
     Hum. Mol. Genet. 8:1599-1610(1999).
     PubMed=10441322
[ 3] Sapir T., Horesh D., Caspi M., Atlas R., Burgess H.A., Wolf S.G.,
     Francis F., Chelly J., Elbaum M., Pietrokovski S., Reiner O.
     "Doublecortin mutations cluster in evolutionarily conserved functional
     domains."
     Hum. Mol. Genet. 9:703-712(2000).
     PubMed=10749977
[ 4] Burgess H.A., Martinez S., Reiner O.
     "KIAA0369, doublecortin-like kinase, is expressed during brain
     development."
     J. Neurosci. Res. 58:567-575(1999).
     PubMed=10533048
[ 5] Guillonneau X., Piriev N.I., Danciger M., Kozak C.A., Cideciyan A.V.,
     Jacobson S.G., Farber D.B.
     "A nonsense mutation in a novel gene is associated with retinitis
     pigmentosa in a family linked to the RP1 locus."
     Hum. Mol. Genet. 8:1541-1546(1999).
     PubMed=10401003

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