X-linked lissencephaly is a severe brain malformation affecting males.
Recently it has been demonstrated that the doublecortin gene is implicated in
this disorder . Doublecortin was found to bind to the microtubule
cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilizes
microtubules and causes bundling . 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 . It has
been suggested that the first DC domain of Doublecortin binds tubulin and
enhances microtubule polymerization .
Some proteins known to contain a DC domain are listed below:
Doublecortin. It is required for neuronal migration . A large number of
point mutations in the human DCX gene leading to lissencephaly are located
within the DC domains .
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 .
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 .
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
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.
Horesh D. Sapir T. Francis F. Wolf S.G. Caspi M. Elbaum M. Chelly J. Reiner O.
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