Doublecortin domain-containing protein 1 (DCDC1), also known as DCDC5, is a member of doublecortin (DCX) family. It is a microtubule-associated protein (MAP) with stable double tandem DCX repeats of ubiquitin-like tertiary fold. DCDC1 is expressed during mitosis and is involved in coordinating late cytokinesis. DCDC1 interacts with cytoplasmic dynein and Rab8, as well as with the Rab8 nucleotide exchange factor Rabin8 [].
FBXW5 is a F-box protein and a DDB1-binding WD40 (DWD) protein that serves as a substrate recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes [, ]. It has also been shown to negatively regulate TAK1 MAP3K in the IL-1beta signaling pathway []. Interestingly, FBXW5 binds centriolar protein HsSAS-6 and promotes its ubiquitylation; this way FBXW5 can restrict centrosome re-duplication through degradation of HsSAS-6 [].
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 stabilises 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, 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 [].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 controlling neuronal migration in the developing brain [, ].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 [, ].
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 stabilises 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, 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 [].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 controlling neuronal migration in the developing brain [, ].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 [, ].
