Doublecortin (DCX)

DCX (doublecortin, N-GST chimera)contains 2 doublecortin domains and belongs to the doublecortin family. It is highly expressed in neuronal cells of fetal brain, but not expressed in other fetal tissues. In the adult, it is highly expressed in the brain frontal lobe, but very low expression in other regions of brain, and not detected in heart, placenta, lung, liver, skeletal muscles, kidney and pancreas. DCX is a microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. It may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein. DCX may in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. It may be part with LIS-1 of a overlapping, but distinct, signaling pathways that promote neuronal migration. Defects in DCX are the cause of lissencephaly X-linked type 1 and subcortical band heterotopia X-linked.

Doublecortin (DCX) Related Areas

Signal Transduction>>Calcium Signaling>>Calcium Binding Protein>>DCX

Doublecortin (DCX) Alternative Names

DBCN, DC, LISX, SCLH, XLIS, doublecortex, doubling, lis-X, lissencephalin-X, neuronal migration protein doublecortin [Homo sapiens]

Dbct, doublecortex, doubling, lis-X, lissencephalin-X, lissencephaly, X-linked (doublecortin), neuronal migration protein doublecortin [Mus musculus]

Summaries for Doublecortin (DCX)

Entrez Gene summary for Doublecortin (DCX):

DCX gene encodes a member of the doublecortin family. The protein encoded by DCX gene is a cytoplasmic protein and contains two doublecortin domains, which bind microtubules. In the developing cortex, cortical neurons must migrate over long distances to reach the site of their final differentiation. The encoded protein appears to direct neuronal migration by regulating the organization and stability of microtubules. In addition, the encoded protein interacts with LIS1, the regulatory gamma subunit of platelet activating factor acetylhydrolase, and this interaction is important to proper microtubule function in the developing cortex. Mutations in this gene cause abnormal migration of neurons during development and disrupt the layering of the cortex, leading to epilepsy, mental retardation, subcortical band heterotopia ("double cortex" syndrome) in females and lissencephaly ("smooth brain" syndrome) in males. Multiple transcript variants encoding different isoforms have been found for DCX gene. [provided by RefSeq, Sep 2010]

Wikipedia summary for Doublecortin (DCX):

Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.

Human Doublecortin (DCX) Protein General Information

 

• Protein names: Doublecortin
• Sequence length: 441 AA.
• Domain: Repeat
• Sequence similarities: Contains 2 doublecortin domains.
• Post-translational modification: Phosphorylation by MARK1, MARK2 and PKA regulates its ability to bind mirotubules.
• Subunit structure: Interacts with tubulin.
• Subcellular location: Cytoplasm. Cell projection . Note: Localizes at neurite tips .
• Tissue specificity: Highly expressed in neuronal cells of fetal brain (in the majority of cells of the cortical plate, intermediate zone and 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, and not detected in heart, placenta, lung, liver, skeletal muscles, kidney and pancreas.
• Involvement in disease: Defects in DCX are the cause of lissencephaly X-linked type 1 (LISX1) ; also called X-LIS or LIS. LISX1 is a classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.
  Defects in DCX are the cause of subcortical band heterotopia X-linked (SBHX) ; also known as double cortex or subcortical laminar heterotopia (SCLH). SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
  Note=A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
• Sequence caution: The sequence CAI39489.1 differs from that shown. Reason: Erroneous initiation.
  The sequence CAI43156.1 differs from that shown. Reason: Erroneous initiation.
  The sequence EAX02644.1 differs from that shown. Reason: Erroneous initiation.

General information above from UniProt

Function for Doublecortin (DCX) Protein

UniProtKB:

Doublecortin is microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. Doublecortin may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein. Doublecortin may in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. Doublecortin may be part with LIS-1 of a overlapping, but distinct, signaling pathways that promote neuronal migration.

Genatlas:

• Doublecortin is involved in calcium dependent signaling of neuronal migration, in binding and stabilization of microtubules
• Doublecortin may direct neuronal migration by regulating the organization and stability of microtubules
• Doublecortin is likely required for neural migration from the ventricular zone to the developing cortex and differentiation
• In addition to vesicular trafficking, doublecortin may play a role in the regulation of cell adhesion via its interaction with USP9X in migrating and differentiating neurons
• Doublecortin acts as a molecular link between microtubule and actin cytoskeletal filaments that is regulated by phosphorylation and PPP1R9B
• Doublecortin is required for nuclear translocation and maintenance of bipolar morphology during migration of the cells and have a critical function in the movement of newly generated neurons in the adult brain
• Doublecortin has important functions in the major migratory pathway in the developing forebrain (Bai 2008)

Homology for human Doublecortin (DCX)

• ortholog to DCX, Pan troglodytes
• homolog to dclk2, Danio rerio
• ortholog to Dcx, mus musculus
• ortholog to Dcx, Rattus norvegicus

Phenotype Information for Doublecortin (DCX)

• Gene/Locus: DCX, DBCN, LISX
• Phenotype: Lissencephaly, X-linked
  Subcortical laminal heteropia, X-linked

Phenotype Information for Doublecortin (DCX) from OMIM (Online Mendelian Inheritance in Man)