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32  structures 479  species 0  interactions 6162  sequences 98  architectures

Family: DCX (PF03607)

Summary: Doublecortin

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This is the Wikipedia entry entitled "Doublecortin". More...

Doublecortin Edit Wikipedia article

Protein DCX PDB 1mjd.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesDCX, DBCN, DC, LISX, SCLH, XLIS, doublecortin
External IDsOMIM: 300121 MGI: 1277171 HomoloGene: 7683 GeneCards: DCX
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for DCX
Genomic location for DCX
BandXq23Start111,293,779 bp[1]
End111,412,429 bp[1]
RNA expression pattern
PBB GE DCX 204850 s at fs.png

PBB GE DCX 204851 s at fs.png
More reference expression data
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr X: 111.29 – 111.41 MbChr X: 143.86 – 143.93 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.[5]


Doublecortin expression in the rat dentate gyrus, 21st postnatal day. Oomen et al., 2009.[6]

Doublecortin (DCX) is a microtubule-associated protein expressed by neuronal precursor cells and immature neurons in embryonic and adult cortical structures. Neuronal precursor cells begin to express DCX while actively dividing, and their neuronal daughter cells continue to express DCX for 2–3 weeks as the cells mature into neurons. Downregulation of DCX begins after 2 weeks, and occurs at the same time that these cells begin to express NeuN, a marker for mature neurons.[7]

Due to the nearly exclusive expression of DCX in developing neurons, this protein has been used increasingly as a marker for neurogenesis. Indeed, levels of DCX expression increase in response to exercise,[8] and that increase occurs in parallel with increased BrdU labeling, which is currently a "gold standard" in measuring neurogenesis.

Doublecortin was found to bind to the microtubule cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilizes microtubules and causes bundling.[9] Doublecortin is a basic protein with an iso-electric point of 10 typical of microtubule-binding proteins.

Knock out mouse

Double layer hippocampus seen in Doublecortin knock out mice (right panels) compared to the normal hippocampus in wild type mice (left panels). Figure extracted from the work of the laboratory of Fiona Francis

In mice where the Doublecortin gene has been knocked out, cortical layers are still correctly formed. However, the hippocampi of these mice show disorganisation in the CA3 region. The normally single layer of pyramidal cells in mutants is seen as a double layer. These mice also have different behavior than their wild type littermates and are epileptic.[10]


PDB 1uf0 EBI.jpg
solution structure of the N-terminal dcx domain of human doublecortin-like kinase

The detailed sequence analysis of Doublecortin and Doublecortin-like proteins allowed the identification of a tandem repeat of evolutionarily conserved Doublecortin (DC) domains. These domains are found in the N terminus of proteins and consists of 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.[11]

Doublecortin has been shown to influence the structure of microtubules. Microtubule nucleated in vitro in the presence of Doublecortin have almost exclusively 13 protofilaments, whereas microtubule nucleated without Doublecortin are present in a range of different sizes.


Doublecortin has been shown to interact with PAFAH1B1.[12]

Clinical significance

Doublecortin is mutated in X-linked lissencephaly and the double cortex syndrome, and the clinical manifestations are sex-linked. In males, X-linked lissencephaly produces a smooth brain due to lack of migration of immature neurons, which normally promote folding of the brain surface. Double cortex syndrome is characterized by abnormal migration of neural tissue during development which results in two bands of misplaced neurons within the subcortical white, generating two cortices, giving the name to the syndrome; this finding generally occurs in females.[13] The mutation was discovered by Joseph Gleeson and Christopher A. Walsh in Boston.[14][15]

See also


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000077279 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031285 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ EntrezGene 1641
  6. ^ Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joëls M, Lucassen PJ (2009). "Opposite effects of early maternal deprivation on neurogenesis in male versus female rats". PLoS ONE. 4 (1): e3675. doi:10.1371/journal.pone.0003675. PMC 2629844. PMID 19180242.
  7. ^ Brown JP, Couillard-Després S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (December 2003). "Transient expression of doublecortin during adult neurogenesis". J. Comp. Neurol. 467 (1): 1–10. doi:10.1002/cne.10874. PMID 14574675.
  8. ^ Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, Bogdahn U, Winkler J, Kuhn HG, Aigner L (January 2005). "Doublecortin expression levels in adult brain reflect neurogenesis". Eur. J. Neurosci. 21 (1): 1–14. doi:10.1111/j.1460-9568.2004.03813.x. PMID 15654838.
  9. ^ Horesh D, Sapir T, Francis F, Wolf SG, Caspi M, Elbaum M, Chelly J, Reiner O (September 1999). "Doublecortin, a stabilizer of microtubules". Hum. Mol. Genet. 8 (9): 1599–610. doi:10.1093/hmg/8.9.1599. PMID 10441322.
  10. ^ Nosten-Bertrand M, Kappeler C, Dinocourt C, Denis C, Germain J, Phan Dinh Tuy F, Verstraeten S, Alvarez C, Métin C, Chelly J, Giros B, Miles R, Depaulis A, Francis F (2008-06-25). "Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus". PLOS ONE. 3 (6): e2473. doi:10.1371/journal.pone.0002473. PMC 2429962. PMID 18575605.
  11. ^ Sapir T, Horesh D, Caspi M, Atlas R, Burgess HA, Wolf SG, Francis F, Chelly J, Elbaum M, Pietrokovski S, Reiner O (March 2000). "Doublecortin mutations cluster in evolutionarily conserved functional domains". Hum. Mol. Genet. 9 (5): 703–12. doi:10.1093/hmg/9.5.703. PMID 10749977.
  12. ^ Caspi M, Atlas R, Kantor A, Sapir T, Reiner O (September 2000). "Interaction between LIS1 and doublecortin, two lissencephaly gene products". Hum. Mol. Genet. 9 (15): 2205–13. doi:10.1093/oxfordjournals.hmg.a018911. PMID 11001923.
  13. ^ Online Mendelian Inheritance in Man (OMIM) Doublecortin -300121
  14. ^ Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA (January 1998). "Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein". Cell. 92 (1): 63–72. doi:10.1016/S0092-8674(00)80899-5. PMID 9489700.
  15. ^ Lowenstein DH (2011). "Seizures and Epilepsy". In Loscalzo J, Longo DL, Fauci AS, Kasper DL, Hauser SL (eds.). Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. pp. 3251–3269. ISBN 978-0-07-174889-6.

Further reading

External links

This article incorporates text from the public domain Pfam and InterPro: IPR003533

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Doublecortin Provide feedback

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Internal database links

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This tab holds annotation information from the InterPro database.

InterPro entry IPR003533

X-linked lissencephaly is a severe brain malformation affecting males. Recently it has been demonstrated that the doublecortin gene is implicated in this disorder [ PUBMED:9489699 ]. Doublecortin was found to bind to the microtubule cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilises microtubules and causes bundling [ PUBMED:10441322 ]. 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 [ PUBMED:10749977 ].

Some proteins known to contain a DC domain are listed below:

  • Doublecortin. It is required for neuronal migration [ PUBMED:9489699 ]. A large number of point mutations in the human DCX gene leading to lissencephaly are located within the DC domains [ PUBMED:10749977 ].
  • 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 [ PUBMED:10533048 ].
  • 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 [ PUBMED:10401003 ].

Gene Ontology

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Seed source: PROSITE
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Griffiths-Jones SR
Number in seed: 217
Number in full: 6162
Average length of the domain: 59.20 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 14.88 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 22.0 22.0
Noise cut-off 21.9 21.9
Model length: 60
Family (HMM) version: 19
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DCX domain has been found. There are 32 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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