PROSITE documentation PDOC50309

Doublecortin domain profile

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].