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PROSITE documentation PDOC50309Doublecortin domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC50309
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].
December 2001 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | 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. |
| Source | Cell 92:51-61(1998). |
| 2 | Authors | Horesh D. Sapir T. Francis F. Wolf S.G. Caspi M. Elbaum M. Chelly J. Reiner O. |
| Title | Doublecortin, a stabilizer of microtubules. | |
| Source | Hum. Mol. Genet. 8:1599-1610(1999). | |
| PubMed ID | 10441322 |
| 3 | Authors | Sapir T. Horesh D. Caspi M. Atlas R. Burgess H.A. Wolf S.G. Francis F. Chelly J. Elbaum M. Pietrokovski S. Reiner O. |
| Title | Doublecortin mutations cluster in evolutionarily conserved functional domains. | |
| Source | Hum. Mol. Genet. 9:703-712(2000). | |
| PubMed ID | 10749977 |
| 4 | Authors | Burgess H.A. Martinez S. Reiner O. |
| Title | KIAA0369, doublecortin-like kinase, is expressed during brain development. | |
| Source | J. Neurosci. Res. 58:567-575(1999). | |
| PubMed ID | 10533048 |
| 5 | Authors | Guillonneau X. Piriev N.I. Danciger M. Kozak C.A. Cideciyan A.V. Jacobson S.G. Farber D.B. |
| Title | A nonsense mutation in a novel gene is associated with retinitis pigmentosa in a family linked to the RP1 locus. | |
| Source | Hum. Mol. Genet. 8:1541-1546(1999). | |
| PubMed ID | 10401003 |
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