O43602 (DCX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuronal migration protein doublecortin

Alternative name(s):
Doublin
Lissencephalin-X
Short name=Lis-X

Gene names

Name:	DCX
Synonyms:	DBCN, LISX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	441 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. 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. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration. Ref.8
Subunit structure	Interacts with tubulin.
Subcellular location	Cytoplasm. Cell projection By similarity. Note: Localizes at neurite tips By similarity.
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.
Post-translational modification	Phosphorylation by MARK1, MARK2 and PKA regulates its ability to bind microtubules By similarity. Phosphorylation at Ser-346 and Ser-378 seems to occur only in neonatal brain, the levels falling precipitously by postnatal day 21 By similarity.
Involvement in disease	Lissencephaly, X-linked 1 (LISX1) [MIM:300067]: 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'. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.10 Ref.11 Ref.19 Ref.22 Subcortical band heterotopia X-linked (SBHX) [MIM:300067]: 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: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
Sequence similarities	Contains 2 doublecortin domains.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell projection Cytoplasm Microtubule
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Epilepsy Lissencephaly
Domain	Repeat
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon extension Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement. Source: Reactome brain development Inferred from electronic annotation. Source: Compara central nervous system development Traceable author statement Ref.1. Source: ProtInc central nervous system projection neuron axonogenesis Inferred from electronic annotation. Source: Compara dendrite morphogenesis Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro neuron migration Inferred from direct assay PubMed 14741102. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome microtubule Inferred from electronic annotation. Source: UniProtKB-KW microtubule associated complex Traceable author statement PubMed 11001923. Source: ProtInc neuron projection Inferred from direct assay PubMed 14741102. Source: UniProtKB
Molecular_function	microtubule binding Inferred from direct assay PubMed 14741102. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoform LIS-XA possesses an alternative exon in 5' and is then translated from an upstream initiation codon. Isoform LIS-XB, isoform LIS-XC and isoform LIS-XD translation starts at the downstream initiation codon, leading to the absence of the 81 first amino acids. Isoform LIS-XC and isoform LIS-XD differ from isoform LIS-XB by a five amino acids and a one amino acid-insertion respectively.

Isoform 1 (identifier: O43602-1)

Also known as: LIS-XA;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43602-2)

Also known as: LIS-XB;

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.

Isoform 3 (identifier: O43602-3)

Also known as: LIS-XC;

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.
     391-391: S → SGNDQD

Isoform 4 (identifier: O43602-4)

Also known as: LIS-XD;

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.
     405-405: S → SV

Isoform 5 (identifier: O43602-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.
     391-391: S → SGN

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 441

441

Neuronal migration protein doublecortin

PRO_0000079833

Regions

Domain

134 – 220

87

Doublecortin 1

Domain

261 – 344

84

Doublecortin 2

Compositional bias

368 – 418

51

Pro/Ser-rich

Amino acid modifications

Modified residue

95

1

Phosphothreonine; by PKC Potential

Modified residue

109

1

Phosphoserine; by CDK5 By similarity

Modified residue

128

1

Phosphoserine; by MARK1 and PKA By similarity

Modified residue

151

1

Phosphotyrosine; by ABL Potential

Modified residue

155

1

Phosphoserine; by PKC Potential

Modified residue

171

1

Phosphoserine; by CK2 Potential

Modified residue

191

1

Phosphoserine; by PKC Potential

Modified residue

196

1

Phosphoserine; by CK2, MARK1 and PKA By similarity

Modified residue

346

1

Phosphoserine; by CK2 By similarity

Modified residue

368

1

Phosphoserine; by CDK5 By similarity

Modified residue

370

1

Phosphothreonine; by CDK5 By similarity

Modified residue

375

1

Phosphoserine; by PKC Potential

Modified residue

378

1

Phosphoserine; by CDK5; alternate By similarity

Modified residue

385

1

Phosphoserine By similarity

Modified residue

387

1

Phosphoserine; by CK2; alternate Potential

Modified residue

387

1

Phosphoserine; by DYRK2; alternate Ref.8

Modified residue

398

1

Phosphoserine By similarity

Modified residue

402

1

Phosphothreonine; by CDK5; alternate By similarity

Modified residue

402

1

Phosphothreonine; by PKC and MAPK; alternate Potential

Modified residue

408

1

Phosphoserine; by CDK5; alternate By similarity

Modified residue

408

1

Phosphoserine; by MAPK; alternate Potential

Modified residue

412

1

Phosphothreonine; by MAPK Potential

Modified residue

415

1

Phosphoserine; by CDK5; alternate By similarity

Modified residue

415

1

Phosphoserine; by MAPK; alternate Potential

Modified residue

418

1

Phosphoserine; by PKC Potential

Modified residue

430

1

Phosphoserine; by CK2 Potential

Modified residue

436

1

Phosphoserine; by CK2 Potential

Natural variations

Alternative sequence

1 – 81

81

Missing in isoform 2, isoform 3, isoform 4 and isoform 5.

VSP_004186

Alternative sequence

391

1

S → SGNDQD in isoform 3.

VSP_004187

Alternative sequence

391

1

S → SGN in isoform 5.

VSP_026375

Alternative sequence

405

1

S → SV in isoform 4.

VSP_004188

Natural variant

123

1

T → I in LISX1. Ref.22

VAR_026022

Natural variant

124

1

L → S in LISX1. Ref.11

VAR_007819

Natural variant

128

1

S → R in LISX1 and SBHX. Ref.2 Ref.18

VAR_007820

Natural variant

131

1

K → N in SBHX. Ref.17

VAR_026023

Natural variant

140

1

R → H in SBHX. Ref.18

VAR_007822

Natural variant

140

1

R → L in LISX1 and SBHX. Ref.2

VAR_007821

Natural variant

141

1

N → D in LISX1. Ref.22

VAR_026024

Natural variant

143

1

D → N in LISX1 and SBHX. Ref.1

VAR_007823

Natural variant

148

1

G → E in SBHX. Ref.20

VAR_026025

Natural variant

152

1

A → S in LISX1. Ref.22

VAR_026026

Natural variant

159

1

R → H in SBH. Ref.15

VAR_010202

Natural variant

159

1

R → L in SBHX. Ref.10 Ref.18

VAR_007824

Natural variant

167

1

D → H in SBHX. Ref.18

VAR_007825

Natural variant

170

1

R → G in SBHX; mild. Ref.15 Ref.18

VAR_010536

Natural variant

178

1

L → R in SBHX. Ref.18

VAR_026027

Natural variant

181

1

G → A in LISX1 and SBHX. Ref.10 Ref.18

VAR_007826

Natural variant

183

1

R → S in LISX1. Ref.11

VAR_007827

Natural variant

185

1

I → T in SBHX. Ref.18

VAR_026028

Natural variant

206

1

Y → D in SBHX. Ref.12

VAR_007829

Natural variant

206

1

Y → H in LISX1 and SBHX. Ref.1

VAR_007828

Natural variant

259

1

R → C in SBHX. Ref.20

VAR_026029

Natural variant

259

1

R → L in SBHX.

VAR_007830

Natural variant

267

1

R → C in SBHX. Ref.10 Ref.14 Ref.18

VAR_007831

Natural variant

272

1

P → L in SBHX.

VAR_026030

Natural variant

272

1

P → R in SBHX.

VAR_007832

Natural variant

273

1

R → W in LISX1 and SBHX. Ref.1 Ref.18

VAR_007833

Natural variant

277

1

R → H in LISX1. Ref.18 Ref.19
Corresponds to variant rs56030372 [ dbSNP | Ensembl ].

VAR_026031

Natural variant

277

1

R → S in epilepsy; resistant partial seizures; related to 'cryptogenic' epilepsy. Ref.21

VAR_026032

Natural variant

281

1

N → I in SBHX. Ref.18

VAR_026033

Natural variant

281

1

N → K in SBHX. Ref.10 Ref.18

VAR_007834

Natural variant

284

1

T → A in SBHX. Ref.18

VAR_026034

Natural variant

284

1

T → R in LISX1 and SBHX. Ref.2 Ref.18

VAR_007835

Natural variant

295

1

I → T in SBHX. Ref.18

VAR_007836

Natural variant

303

1

T → I in SBHX.

VAR_007837

Natural variant

304

1

G → E in SBHX. Ref.12

VAR_007838

Natural variant

304

1

G → V in SBHX. Ref.18

VAR_026035

Natural variant

317

1

V → I in SBHX.

VAR_007839

Natural variant

324

1

F → L in LISX1. Ref.22

VAR_026036

Natural variant

331

1

I → N in SBHX.

VAR_007840

Natural variant

331

1

I → T in SBHX. Ref.12

VAR_007841

Natural variant

332

1

A → S in SBHX. Ref.18

VAR_026037

Natural variant

332

1

A → V in SBHX. Ref.16

VAR_026038

Natural variant

334

1

G → D in SBHX.

VAR_007842

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

441

Helix Strand Turn

Details...

Beta strand

134 – 140

7

Beta strand

149 – 153

5

Turn

155 – 157

3

Helix

161 – 172

12

Beta strand

175 – 177

3

Beta strand

184 – 187

4

Beta strand

191 – 194

4

Helix

197 – 199

3

Beta strand

205 – 213

9

Turn

225 – 227

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (LIS-XA) [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 945988E263F261CD	FASTA	441	49,318
	10 20 30 40 50 60 MKTLPLHSHC TEMQRLLPKL EMLTLGSSFC SLQGEFCQAM DSFTTVSHVG MCEETDASFN 70 80 90 100 110 120 VFSPKFQFDR SHCQSLRFHQ NMELDFGHFD ERDKTSRNMR GSRMNGLPSP THSAHCSFYR 130 140 150 160 170 180 TRTLQALSNE KKAKKVRFYR NGDRYFKGIV YAVSSDRFRS FDALLADLTR SLSDNINLPQ 190 200 210 220 230 240 GVRYIYTIDG SRKIGSMDEL EEGESYVCSS DNFFKKVEYT KNVNPNWSVN VKTSANMKAP 250 260 270 280 290 300 QSLASSNSAQ ARENKDFVRP KLVTIIRSGV KPRKAVRVLL NKKTAHSFEQ VLTDITEAIK 310 320 330 340 350 360 LETGVVKKLY TLDGKQVTCL HDFFGDDDVF IACGPEKFRY AQDDFSLDEN ECRVMKGNPS 370 380 390 400 410 420 ATAGPKASPT PQKTSAKSPG PMRRSKSPAD SANGTSSSQL STPKSKQSPI STPTSPGSLR 430 440 KHKDLYLPLS LDDSDSLGDS M
	Isoform 2 (LIS-XB) [UniParc]. Checksum: 91D0D89433AF52A0	FASTA	360	40,044
	10 20 30 40 50 60 MELDFGHFDE RDKTSRNMRG SRMNGLPSPT HSAHCSFYRT RTLQALSNEK KAKKVRFYRN 70 80 90 100 110 120 GDRYFKGIVY AVSSDRFRSF DALLADLTRS LSDNINLPQG VRYIYTIDGS RKIGSMDELE 130 140 150 160 170 180 EGESYVCSSD NFFKKVEYTK NVNPNWSVNV KTSANMKAPQ SLASSNSAQA RENKDFVRPK 190 200 210 220 230 240 LVTIIRSGVK PRKAVRVLLN KKTAHSFEQV LTDITEAIKL ETGVVKKLYT LDGKQVTCLH 250 260 270 280 290 300 DFFGDDDVFI ACGPEKFRYA QDDFSLDENE CRVMKGNPSA TAGPKASPTP QKTSAKSPGP 310 320 330 340 350 360 MRRSKSPADS ANGTSSSQLS TPKSKQSPIS TPTSPGSLRK HKDLYLPLSL DDSDSLGDSM
	Isoform 3 (LIS-XC) [UniParc]. Checksum: 1E859F2114CC3BB1	FASTA	365	40,574
	10 20 30 40 50 60 MELDFGHFDE RDKTSRNMRG SRMNGLPSPT HSAHCSFYRT RTLQALSNEK KAKKVRFYRN 70 80 90 100 110 120 GDRYFKGIVY AVSSDRFRSF DALLADLTRS LSDNINLPQG VRYIYTIDGS RKIGSMDELE 130 140 150 160 170 180 EGESYVCSSD NFFKKVEYTK NVNPNWSVNV KTSANMKAPQ SLASSNSAQA RENKDFVRPK 190 200 210 220 230 240 LVTIIRSGVK PRKAVRVLLN KKTAHSFEQV LTDITEAIKL ETGVVKKLYT LDGKQVTCLH 250 260 270 280 290 300 DFFGDDDVFI ACGPEKFRYA QDDFSLDENE CRVMKGNPSA TAGPKASPTP QKTSAKSPGP 310 320 330 340 350 360 MRRSKSPADS GNDQDANGTS SSQLSTPKSK QSPISTPTSP GSLRKHKDLY LPLSLDDSDS LGDSM
	Isoform 4 (LIS-XD) [UniParc]. Checksum: 8DE5D9AE42D08AAF	FASTA	361	40,143
	10 20 30 40 50 60 MELDFGHFDE RDKTSRNMRG SRMNGLPSPT HSAHCSFYRT RTLQALSNEK KAKKVRFYRN 70 80 90 100 110 120 GDRYFKGIVY AVSSDRFRSF DALLADLTRS LSDNINLPQG VRYIYTIDGS RKIGSMDELE 130 140 150 160 170 180 EGESYVCSSD NFFKKVEYTK NVNPNWSVNV KTSANMKAPQ SLASSNSAQA RENKDFVRPK 190 200 210 220 230 240 LVTIIRSGVK PRKAVRVLLN KKTAHSFEQV LTDITEAIKL ETGVVKKLYT LDGKQVTCLH 250 260 270 280 290 300 DFFGDDDVFI ACGPEKFRYA QDDFSLDENE CRVMKGNPSA TAGPKASPTP QKTSAKSPGP 310 320 330 340 350 360 MRRSKSPADS ANGTSSSQLS TPKSVKQSPI STPTSPGSLR KHKDLYLPLS LDDSDSLGDS M
	Isoform 5 [UniParc]. Checksum: 1E144731B8671F4B	FASTA	362	40,215
	10 20 30 40 50 60 MELDFGHFDE RDKTSRNMRG SRMNGLPSPT HSAHCSFYRT RTLQALSNEK KAKKVRFYRN 70 80 90 100 110 120 GDRYFKGIVY AVSSDRFRSF DALLADLTRS LSDNINLPQG VRYIYTIDGS RKIGSMDELE 130 140 150 160 170 180 EGESYVCSSD NFFKKVEYTK NVNPNWSVNV KTSANMKAPQ SLASSNSAQA RENKDFVRPK 190 200 210 220 230 240 LVTIIRSGVK PRKAVRVLLN KKTAHSFEQV LTDITEAIKL ETGVVKKLYT LDGKQVTCLH 250 260 270 280 290 300 DFFGDDDVFI ACGPEKFRYA QDDFSLDENE CRVMKGNPSA TAGPKASPTP QKTSAKSPGP 310 320 330 340 350 360 MRRSKSPADS GNANGTSSSQ LSTPKSKQSP ISTPTSPGSL RKHKDLYLPL SLDDSDSLGD SM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome." 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. Cell 92:51-61(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 4), VARIANTS LISX1 ASN-143; HIS-206 AND TRP-273. Tissue: Fetal brain.
[2]	"Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein." Gleeson J.G., Allen K.M., Fox J.W., Lamperti E.D., Berkovic S., Scheffer I., Cooper E.C., Dobyns W.B., Minnerath S.R., Ross M.E., Walsh C.A. Cell 92:63-72(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANTS LISX1 ARG-128; LEU-140 AND ARG-284. Tissue: Brain.
[3]	"X-linked neuronal migration disorder (lissencephaly/subcortical band heterotopia) is caused by mutation in a novel brain-specific protein, lissencephalin-X." Sossey-Alaoui K., Srivastava A.K. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Fetal brain.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization, and neuronal morphology." Slepak T.I., Salay L.D., Lemmon V.P., Bixby J.L. Cytoskeleton 69:514-527(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-387.
[9]	"The DCX-domain tandems of doublecortin and doublecortin-like kinase." Kim M.H., Cierpicki T., Derewenda U., Krowarsch D., Feng Y., Devedjiev Y., Dauter Z., Walsh C.A., Otlewski J., Bushweller J.H., Derewenda Z.S. Nat. Struct. Biol. 10:324-333(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 126-231.
[10]	"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." Sossey-Alaoui K., Hartung A.J., Guerrini R., Manchester D.K., Posar A., Puche-Mira A., Andermann E., Dobyns W.B., Srivastava A.K. Hum. Mol. Genet. 7:1327-1332(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LISX1/SBHX LEU-159; ALA-181; CYS-267 AND LYS-281.
[11]	"LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation." Pilz D.T., Matsumoto N., Minnerath S.R., Mills P., Gleeson J.G., Allen K.M., Walsh C.A., Barkovich A.J., Dobyns W.B., Ledbetter D.H., Ross M.E. Hum. Mol. Genet. 7:2029-2037(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LISX1 SER-124 AND SER-183.
[12]	"Doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)." Des Portes V., Francis F., Pinard J.-M., Desguerre I., Moutard M.-L., Snoeck I., Meiners L.C., Capron F., Cusmai R., Ricci S., Motte J., Echenne B., Ponsot G., Dulac O., Chelly J., Beldjord C. Hum. Mol. Genet. 7:1063-1070(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SBHX ASP-206; GLU-304 AND THR-331.
[13]	"Characterization of mutations in the gene doublecortin in patients with double cortex syndrome." Gleeson J.G., Minnerath S.R., Fox J.W., Allen K.M., Luo R.F., Hong S.E., Berg M.J., Kuzniecky R., Reitnauer P.J., Borgatti R., Puche-Mira A., Guerrini R., Holmes G.L., Rooney C.M., Berkovic S., Scheffer I., Cooper E.C., Ricci S. , Cusmai R., Crawford T.O., Leroy R., Andermann E., Wheless J.W., Dobyns W.B., Ross M.E., Walsh C.A. Ann. Neurol. 45:146-153(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SBHX.
[14]	"A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia." Kato M., Kimura T., Lin C., Ito A., Kodama S., Morikawa T., Soga T., Hayasaka K. Hum. Genet. 104:341-344(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SBHX CYS-267.
[15]	"Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1." Pilz D.T., Kuc J., Matsumoto N., Bodurtha J., Bernadi B., Tassinari C.A., Dobyns W.B., Ledbetter D.H. Hum. Mol. Genet. 8:1757-1760(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SBHX HIS-159 AND GLY-170.
[16]	"Genetic alteration of the DCX gene in Japanese patients with subcortical laminar heterotopia or isolated lissencephaly sequence." Sakamoto M., Ono J., Okada S., Nakamura Y., Kurahashi H. J. Hum. Genet. 45:167-170(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SBHX VAL-332.
[17]	"Mutation of the doublecortin gene in male patients with double cortex syndrome: somatic mosaicism detected by hair root analysis." Kato M., Kanai M., Soma O., Takusa Y., Kimura T., Numakura C., Matsuki T., Nakamura S., Hayasaka K. Ann. Neurol. 50:547-551(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SBHX ASN-131.
[18]	"Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia." Matsumoto N., Leventer R.J., Kuc J.A., Mewborn S.K., Dudlicek L.L., Ramocki M.B., Pilz D.T., Mills P.L., Das S., Ross M.E., Ledbetter D.H., Dobyns W.B. Eur. J. Hum. Genet. 9:5-12(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SBHX ARG-128; HIS-140; LEU-159; HIS-167; GLY-170; ARG-178; ALA-181; THR-185; CYS-267; TRP-273; HIS-277; ILE-281; LYS-281; ALA-284; ARG-284; THR-295; VAL-304 AND SER-332.
[19]	"Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene." Demelas L., Serra G., Conti M., Achene A., Mastropaolo C., Matsumoto N., Dudlicek L.L., Mills P.L., Dobyns W.B., Ledbetter D.H., Das S. Neurology 57:327-330(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LISX1 HIS-277.
[20]	"Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females." D'Agostino M.D., Bernasconi A., Das S., Bastos A., Valerio R.M., Palmini A., Costa da Costa J., Scheffer I.E., Berkovic S., Guerrini R., Dravet C., Ono J., Gigli G., Federico A., Booth F., Bernardi B., Volpi L., Tassinari C.A. , Guggenheim M.A., Ledbetter D.H., Gleeson J.G., Lopes-Cendes I., Vossler D.G., Malaspina E., Franzoni E., Sartori R.J., Mitchell M.H., Mercho S., Dubeau F., Andermann F., Dobyns W.B., Andermann E. Brain 125:2507-2522(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SBHX GLU-148 AND CYS-259.
[21]	"So-called 'cryptogenic' partial seizures resulting from a subtle cortical dysgenesis due to a doublecortin gene mutation." des Portes V., Abaoub L., Joannard A., Souville I., Francis F., Pinard J.-M., Chelly J., Beldjord C., Jouk P.S. Seizure 11:273-277(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPILEPSY SER-277.
[22]	"Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders." Aigner L., Uyanik G., Couillard-Despres S., Ploetz S., Wolff G., Morris-Rosendahl D., Martin P., Eckel U., Spranger S., Otte J., Woerle H., Holthausen H., Apheshiotis N., Fluegel D., Winkler J. Neurology 60:329-332(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LISX1 ILE-123; ASP-141; SER-152 AND LEU-324.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ003112 mRNA. Translation: CAA05867.1.
AJ005592 , AJ005593, AJ005594, AJ005595, AJ005596, AJ005597 Genomic DNA. Translation: CAA06617.1.
AF034634 mRNA. Translation: AAC52037.1.
AF040254 mRNA. Translation: AAC31797.1.
AF040255 mRNA. Translation: AAC31696.1.
AL031117 Genomic DNA. Translation: CAA19966.3.
AL450490, AL031117 Genomic DNA. Translation: CAI39488.2.
AL450490, AL031117 Genomic DNA. Translation: CAI39489.1.
AL031117, AL450490 Genomic DNA. Translation: CAI43156.1.
CH471120 Genomic DNA. Translation: EAX02644.1.
CH471120 Genomic DNA. Translation: EAX02645.1.
CH471120 Genomic DNA. Translation: EAX02642.1.
CH471120 Genomic DNA. Translation: EAX02643.1.
CH471120 Genomic DNA. Translation: EAX02646.1.
CH471120 Genomic DNA. Translation: EAX02647.1.
CH471120 Genomic DNA. Translation: EAX02649.1.
BC027925 mRNA. Translation: AAH27925.1.

IPI

IPI00216744.
IPI00220076.
IPI00220077.
IPI00220078.
IPI00847840.

RefSeq

NP_000546.2. NM_000555.3.
NP_835364.1. NM_178151.2.
NP_835365.1. NM_178152.2.
NP_835366.1. NM_178153.2.

UniGene

Hs.34780.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MJD	NMR	-	A	126-231	[»]
2BQQ	X-ray	2.20	A	126-231	[»]
2XRP	electron microscopy	8.20	I	127-221	[»]
4ATU	electron microscopy	8.30	I	83-441	[»]

ProteinModelPortal

O43602.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000337697.

PTM databases

PhosphoSite

O43602.

Proteomic databases

PaxDb

O43602.

PRIDE

O43602.

Protocols and materials databases

DNASU

1641.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338081; ENSP00000337697; ENSG00000077279.
ENST00000356220; ENSP00000348553; ENSG00000077279.
ENST00000356915; ENSP00000349385; ENSG00000077279.
ENST00000371993; ENSP00000361061; ENSG00000077279.
ENST00000488120; ENSP00000419861; ENSG00000077279.

GeneID

1641.

KEGG

hsa:1641.

UCSC

uc004epd.3. human.

Organism-specific databases

CTD

1641.

GeneCards

GC0XM110537.

HGNC

HGNC:2714. DCX.

HPA

CAB012243.

MIM

300067. phenotype.
300121. gene.

neXtProt

NX_O43602.

Orphanet

2148. Lissencephaly type 1 due to doublecortin gene mutation.

PharmGKB

PA27184.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG238212.

HOVERGEN

HBG003790.

KO

K16579.

OMA

VKASASQ.

OrthoDB

EOG4SJ5F5.

PhylomeDB

O43602.

Enzyme and pathway databases

Pathway_Interaction_DB

lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

O43602.

Bgee

O43602.

CleanEx

HS_DCX.

Genevestigator

O43602.

GermOnline

ENSG00000077279. Homo sapiens.

Family and domain databases

Gene3D

3.10.20.230. 2 hits.

InterPro

IPR017302. Doublecortin_chordata.
IPR003533. Doublecortin_dom.
[Graphical view]

Pfam

PF03607. DCX. 2 hits.
[Graphical view]

PIRSF

PIRSF037870. Doublin. 1 hit.

SMART

SM00537. DCX. 2 hits.
[Graphical view]

SUPFAM

SSF89837. Doublecortin_dom. 2 hits.

PROSITE

PS50309. DC. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DCX. human.

EvolutionaryTrace

O43602.

GenomeRNAi

1641.

NextBio

6740.

SOURCE

Search...

Entry information

Entry name

DCX_HUMAN

Accession

Primary (citable) accession number: O43602
Secondary accession number(s): A6NFY6 , A9Z1V8, D3DUY8, D3DUY9, D3DUZ0, O43911, Q5JYZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.