This is the Wikipedia entry entitled "Doublecortin". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Doublecortin Edit Wikipedia article
PDB rendering based on 1mjd.
|RNA expression pattern|
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.
Due to the nearly exclusive expression of DCX in developing neurons, this protein has been used increasingly as a marker for neurogenesis. Indeed, the levels of DCX expression increase in response to exercise, which occurs in parallel with increased BrdU labelling, 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 stabilises microtubules and causes bundling. Doublecortin is a basic protein with an iso-electric point of 10, typical of microtubule-binding proteins.
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 an 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.
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 is mutated in humans in the syndrome X-linked lissencephaly and double cortex, X-linked lissencephaly means that the disorder produce a smooth brain because of lack of migration of immature neurons, without the normal folds of the brain surface. In the case of double cortex the disease is characterized by abnormal migration during development that results in two bands of misplaced neurons in the subcortical white matter that generate two cortex, giving the name to the syndrome, clinically patients with X-linked lissencephaly, the majority of times are males with a mutation in the their X chromosome. In the case of double cortex the majority of the patients are females with a mutation in one of the X-chromosome, they presents intractable seizures and mental retardation. The severity of the disease can be implied by a gene dosage effect, meaning that in the case of males, with only one X chromosome, there is no protein, however in the case of females with two X chromosome, the mutation in one X chromosome can somehow be compensated, however not enough functional protein is produced in the double cortex patients. The mutation was discovered by Joseph Gleeson and Christopher A. Walsh in Boston.
- EntrezGene 1641
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Online 'Mendelian Inheritance in Man' (OMIM) Doublecortin -300121
- 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.
- Lowenstein DH (2011). "Seizures and Epilepsy". In Loscalzo J, Longo DL, Fauci AS, Kasper DL, Hauser SL. Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. pp. 3251–3269. ISBN 0-07-174889-X.
- des Portes V, Pinard JM, Smadja D, et al. (1997). "Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22.". J. Med. Genet. 34 (3): 177–83. doi:10.1136/jmg.34.3.177. PMC 1050888. PMID 9132485.
- des Portes V, Pinard JM, Billuart P, et al. (1998). "A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.". Cell 92 (1): 51–61. doi:10.1016/S0092-8674(00)80898-3. PMID 9489699.
- Gleeson JG, Allen KM, Fox JW, et al. (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.
- des Portes V, Francis F, Pinard JM, et al. (1999). "doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH).". Hum. Mol. Genet. 7 (7): 1063–70. doi:10.1093/hmg/7.7.1063. PMID 9618162.
- Sossey-Alaoui K, Hartung AJ, Guerrini R, et al. (1998). "Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects.". Hum. Mol. Genet. 7 (8): 1327–32. doi:10.1093/hmg/7.8.1327. PMID 9668176.
- Pilz DT, Matsumoto N, Minnerath S, et al. (1999). "LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation.". Hum. Mol. Genet. 7 (13): 2029–37. doi:10.1093/hmg/7.13.2029. PMID 9817918.
- Gleeson JG, Minnerath SR, Fox JW, et al. (1999). "Characterization of mutations in the gene doublecortin in patients with double cortex syndrome.". Ann. Neurol. 45 (2): 146–53. doi:10.1002/1531-8249(199902)45:2<146::AID-ANA3>3.0.CO;2-N. PMID 9989615.
- Kato M, Kimura T, Lin C, et al. (1999). "A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia.". Hum. Genet. 104 (4): 341–4. doi:10.1007/s004390050963. PMID 10369164.
- Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999). "Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.". Neuron 23 (2): 257–71. doi:10.1016/S0896-6273(00)80778-3. PMID 10399933.
- Pilz DT, Kuc J, Matsumoto N, et al. (2000). "Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.". Hum. Mol. Genet. 8 (9): 1757–60. doi:10.1093/hmg/8.9.1757. PMID 10441340.
- Sakamoto M, Ono J, Okada S, et al. (2000). "Genetic alteration of the DCX gene in Japanese patients with subcortical laminar heterotopia or isolated lissencephaly sequence.". J. Hum. Genet. 45 (3): 167–70. doi:10.1007/s100380050204. PMID 10807542.
- Caspi M, Atlas R, Kantor A, et al. (2001). "Interaction between LIS1 and doublecortin, two lissencephaly gene products.". Hum. Mol. Genet. 9 (15): 2205–13. doi:10.1093/oxfordjournals.hmg.a018911. PMID 11001923.
- Matsumoto N, Leventer RJ, Kuc JA, et al. (2001). "Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.". Eur. J. Hum. Genet. 9 (1): 5–12. doi:10.1038/sj.ejhg.5200548. PMID 11175293.
- Demelas L, Serra G, Conti M, et al. (2001). "Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene.". Neurology 57 (2): 327–30. PMID 11468322.
- Friocourt G, Chafey P, Billuart P, et al. (2001). "Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system.". Mol. Cell. Neurosci. 18 (3): 307–19. doi:10.1006/mcne.2001.1022. PMID 11591131.
- Kato M, Kanai M, Soma O, et al. (2001). "Mutation of the doublecortin gene in male patients with double cortex syndrome: somatic mosaicism detected by hair root analysis.". Ann. Neurol. 50 (4): 547–51. doi:10.1002/ana.1231. PMID 11601509.
- des Portes V, Abaoub L, Joannard A, et al. (2002). "So-called 'cryptogenic' partial seizures resulting from a subtle cortical dysgenesis due to a doublecortin gene mutation.". Seizure : the journal of the British Epilepsy Association 11 (4): 273–7. doi:10.1053/seiz.2001.0607. PMID 12027577.
- Kizhatil K, Wu YX, Sen A, Bennett V (2002). "A new activity of doublecortin in recognition of the phospho-FIGQY tyrosine in the cytoplasmic domain of neurofascin.". J. Neurosci. 22 (18): 7948–58. PMID 12223548.
- D'Agostino MD, Bernasconi A, Das S, et al. (2002). "Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females.". Brain 125 (Pt 11): 2507–22. doi:10.1093/brain/awf248. PMID 12390976.
- Meyer G, Perez-Garcia CG, Gleeson JG (2003). "Selective expression of doublecortin and LIS1 in developing human cortex suggests unique modes of neuronal movement.". Cereb. Cortex 12 (12): 1225–36. doi:10.1093/cercor/12.12.1225. PMID 12427674.
- Media related to doublecortin at Wikimedia Commons
- GeneReviews/NCBI/NIH/UW entry on DCX-Related Disorders
- OMIM entries on DCX-Related Disorders
- doublecortin protein at the US National Library of Medicine Medical Subject Headings (MeSH)
Doublecortin Provide feedback
No Pfam abstract.
External database links
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. 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].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||intracellular signal transduction (GO:0035556)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Number in seed:||53|
|Number in full:||1063|
|Average length of the domain:||60.20 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||14.44 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||12|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
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 7 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 seqence.
Loading structure mapping...