InterPro domain: IPR036572

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 stabilises 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, which is ubiquitin-like. 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 polymerisation [ 3 ].

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

• Doublecortin. It is required for neuronal migration [ 4 ]. A large number of point mutations in the human DCX gene leading to lissencephaly are located within the DC domains [ 4 ].
• Human serine/threonine-protein kinase DCAMKL1. It is a probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain [ 4 , 5 ].
• Retinitis pigmentosa 1 protein. It is required for the differentiation of photoreceptor cells. Mutation in the human RP1 gene cause retinitis pigmentosa of type 1 [ 6 , 7 ].

1. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92, 51-61
2. Doublecortin, a stabilizer of microtubules. Hum. Mol. Genet. 8, 1599-610
3. Doublecortin mutations cluster in evolutionarily conserved functional domains. Hum. Mol. Genet. 9, 703-12
4. KIAA0369, doublecortin-like kinase, is expressed during brain development. J. Neurosci. Res. 58, 567-75
5. Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV. J Biol Chem 281, 20427-39
6. A nonsense mutation in a novel gene is associated with retinitis pigmentosa in a family linked to the RP1 locus. Hum. Mol. Genet. 8, 1541-6
7. Essential and synergistic roles of RP1 and RP1L1 in rod photoreceptor axoneme and retinitis pigmentosa. J. Neurosci. 29, 9748-60