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neuronal migration protein doublecortin; lissencephalin-X; Lis-X; doublin (DCX, DBCN, LISX)

Function: - microtubule-associated protein - seems to be required for initial steps of neuronal dispersion & cortex lamination during cerebral cortex development - may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein - may participate in a signaling pathway that is crucial for neuronal interaction before & during migration, possibly as part of a Ca+2-dependent signal transduction pathway - may be part with LIS-1 of an overlapping, but distinct, signaling pathways that promote neuronal migration - phosphorylation by MARK1, MARK2 & PKA regulates its ability to bind microtubules - phosphorylation at Ser-346 & Ser-378 seems to occur only in neonatal brain; the levels falling precipitously by postnatal day 21 - interacts with tubulin - interacts with USP9X Structure: - contains 2 doublecortin domains Compartment: - cytoplasm, cell projection Alternative splicing: - named isoforms=5 - isoform LIS-XA possesses an alternative exon in 5' & is then translated from an upstream initiation codon - isoform LIS-XB, isoform LIS-XC & isoform LIS-XD translation starts at the downstream initiation codon, resulting in absence of the 81 first amino acids - isoform LIS-XC & isoform LIS-XD differ from isoform LIS-XB by a 5 amino acid & a 1 amino acid-insertion, respectively Expression: - highly expressed in neuronal cells of fetal brain (in the majority of cells of the cortical plate, intermediate zone & ventricular zone), but not expressed in other fetal tissues - in the adult, highly expressed in the brain frontal lobe, but very low expression in other regions of brain, - not detected in heart, placenta, lung, liver, skeletal muscle, kidney & pancreas Pathology: - defects in DCX are the cause of a) lissencephaly X-linked type 1 b) subcortical band heterotopia X-linked - chromosomal translocation t(X;2)(q22.3;p25.1) involving DCX is found in lissencephaly Comparative biology: - expressed in dentate gyrus of female Sprague-Dawley rats - doublecortin positive cells in the dentate gyrus decline 94-97% in old (26 months) vs young (4-6 month) old rats [4]

Related

double cortex/X-linked lissencephaly syndrome; X-linked subcortical laminar heterotopia/lissencephaly syndrome; subcortical band heterotopia X-linked doublecortin or LISX gene

General

microtubule-associated protein (MAP) phosphoprotein

Properties

SIZE: entity length = 441 aa MW = 49 kD COMPARTMENT: cytoplasm MOTIF: Thr phosphorylation site {T95} Ser phosphorylation site {S109} Ser phosphorylation site {S128} doublecortin domain {134-220} MOTIF: Tyr phosphorylation site {Y151} Ser phosphorylation site {S155} Ser phosphorylation site {S171} Ser phosphorylation site {S191} Ser phosphorylation site {S196} doublecortin domain {261-344} Ser phosphorylation site {S346} serine-rich region {368-418} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S368} Thr phosphorylation site {T370} Ser phosphorylation site {S375} Ser phosphorylation site {S378} Ser phosphorylation site {S387} Thr phosphorylation site {T402} Ser phosphorylation site {S408} Thr phosphorylation site {T412} Ser phosphorylation site {S415} Ser phosphorylation site {S418} Ser phosphorylation site {S430} Ser phosphorylation site {S436}

Database Correlations

OMIM correlations MORBIDMAP 300121 UniProt O43602 Pfam PF03607 Entrez Gene 1641 Kegg hsa:1641

References

  1. UniProt :accession O43602
  2. prosite :accession PS50309
  3. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/DCX
  4. Morel GR, Andersen T, Pardo J et al Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats. Neuroscience. 2015 Jun 30;303:189-199. PMID: 26141841