DCX_MOUSE
ID DCX_MOUSE Reviewed; 366 AA.
AC O88809; Q6E5A4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Neuronal migration protein doublecortin;
DE AltName: Full=Doublin;
DE AltName: Full=Lissencephalin-X;
DE Short=Lis-X;
GN Name=Dcx; Synonyms=Dcn;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=9837748; DOI=10.1006/bbrc.1998.9698;
RA Matsuo N., Kawamoto S., Matsubara K., Okubo K.;
RT "Cloning and developmental expression of the murine homolog of
RT doublecortin.";
RL Biochem. Biophys. Res. Commun. 252:571-576(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=9668176; DOI=10.1093/hmg/7.8.1327;
RA Sossey-Alaoui K., Hartung A.J., Guerrini R., Manchester D.K., Posar A.,
RA Puche-Mira A., Andermann E., Dobyns W.B., Srivastava A.K.;
RT "Human doublecortin (DCX) and the homologous gene in mouse encode a
RT putative Ca2+-dependent signaling protein which is mutated in human X-
RT linked neuronal migration defects.";
RL Hum. Mol. Genet. 7:1327-1332(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT SER-28; SER-287; THR-289;
RP SER-297; THR-326; SER-332 AND SER-339, AND MUTAGENESIS OF SER-28; SER-287;
RP THR-289; SER-297; THR-326; SER-332; THR-336 AND SER-339.
RC STRAIN=Swiss Webster; TISSUE=Embryo;
RX PubMed=15099191; DOI=10.1042/bj20040324;
RA Graham M.E., Ruma-Haynes P., Capes-Davis A.G., Dunn J.M., Tan T.C.,
RA Valova V.A., Robinson P.J., Jeffrey P.L.;
RT "Multisite phosphorylation of doublecortin by cyclin-dependent kinase 5.";
RL Biochem. J. 381:471-481(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332 AND SER-339, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP PHOSPHORYLATION AT SER-265 AND SER-297.
RX PubMed=22807455; DOI=10.1002/pmic.201200003;
RA Goswami T., Li X., Smith A.M., Luderowski E.M., Vincent J.J., Rush J.,
RA Ballif B.A.;
RT "Comparative phosphoproteomic analysis of neonatal and adult murine
RT brain.";
RL Proteomics 12:2185-2189(2012).
RN [8]
RP UBIQUITINATION.
RX PubMed=25088421; DOI=10.1016/j.celrep.2014.06.056;
RA Yoshihara S., Takahashi H., Nishimura N., Kinoshita M., Asahina R.,
RA Kitsuki M., Tatsumi K., Furukawa-Hibi Y., Hirai H., Nagai T., Yamada K.,
RA Tsuboi A.;
RT "Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine
RT development of newborn olfactory bulb interneurons.";
RL Cell Rep. 8:843-857(2014).
CC -!- FUNCTION: Microtubule-associated protein required for initial steps of
CC neuronal dispersion and cortex lamination during cerebral cortex
CC development. May act by competing with the putative neuronal protein
CC kinase DCLK1 in binding to a target protein. May in that way
CC participate in a signaling pathway that is crucial for neuronal
CC interaction before and during migration, possibly as part of a calcium
CC ion-dependent signal transduction pathway. May participate along with
CC PAFAH1B1/LIS-1 in a distinct overlapping signaling pathway that
CC promotes neuronal migration. {ECO:0000250|UniProtKB:Q9ESI7}.
CC -!- SUBUNIT: Interacts with tubulin. Interacts with USP9X.
CC {ECO:0000250|UniProtKB:O43602}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cell projection, neuron
CC projection {ECO:0000250|UniProtKB:Q9ESI7}. Note=Localizes at neurite
CC tips. {ECO:0000250|UniProtKB:Q9ESI7}.
CC -!- TISSUE SPECIFICITY: In neonatal tissues, highly expressed in brain, but
CC not expressed in heart, liver, kidney and spleen. In adult tissues,
CC faintly expressed in brain but not expressed in muscle, heart, lung,
CC liver, spleen, intestine, kidney, testis and placenta.
CC -!- DEVELOPMENTAL STAGE: Already expressed by 11 dpc, maximally around
CC birth, expression decreasing gradually during the second postnatal
CC week, with no expression in adult stages.
CC -!- PTM: Phosphorylation by MARK1, MARK2 and PKA regulates its ability to
CC bind microtubules (By similarity). Phosphorylation at Ser-265 and Ser-
CC 297 seems to occur only in neonatal brain, the levels falling
CC precipitously by postnatal day 21 (PubMed:15099191, PubMed:22807455).
CC {ECO:0000250|UniProtKB:Q9ESI7, ECO:0000269|PubMed:15099191,
CC ECO:0000269|PubMed:22807455}.
CC -!- PTM: Ubiquitinated by MDM2, leading to its degradation by the
CC proteasome (PubMed:25088421). Ubiquitinated by MDM2 and subsequent
CC degradation leads to reduce the dendritic spine density of olfactory
CC bulb granule cells (PubMed:25088421). {ECO:0000269|PubMed:25088421}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB011678; BAA33387.1; -; mRNA.
DR EMBL; AF045547; AAC31799.1; -; mRNA.
DR EMBL; AY560329; AAT58219.1; -; mRNA.
DR EMBL; BX530055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS53209.1; -.
DR PIR; JE0368; JE0368.
DR RefSeq; NP_001103692.1; NM_001110222.1.
DR RefSeq; NP_001103693.1; NM_001110223.1.
DR RefSeq; NP_001103694.1; NM_001110224.1.
DR RefSeq; NP_034155.2; NM_010025.2.
DR AlphaFoldDB; O88809; -.
DR BMRB; O88809; -.
DR SMR; O88809; -.
DR BioGRID; 199073; 15.
DR CORUM; O88809; -.
DR IntAct; O88809; 5.
DR STRING; 10090.ENSMUSP00000084570; -.
DR iPTMnet; O88809; -.
DR PhosphoSitePlus; O88809; -.
DR PaxDb; O88809; -.
DR PeptideAtlas; O88809; -.
DR PRIDE; O88809; -.
DR ProteomicsDB; 279319; -.
DR Antibodypedia; 29535; 755 antibodies from 45 providers.
DR DNASU; 13193; -.
DR Ensembl; ENSMUST00000033642; ENSMUSP00000033642; ENSMUSG00000031285.
DR Ensembl; ENSMUST00000087313; ENSMUSP00000084570; ENSMUSG00000031285.
DR GeneID; 13193; -.
DR KEGG; mmu:13193; -.
DR UCSC; uc033jun.1; mouse.
DR CTD; 1641; -.
DR MGI; MGI:1277171; Dcx.
DR VEuPathDB; HostDB:ENSMUSG00000031285; -.
DR eggNOG; KOG3757; Eukaryota.
DR GeneTree; ENSGT00940000161570; -.
DR InParanoid; O88809; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; O88809; -.
DR TreeFam; TF318770; -.
DR BioGRID-ORCS; 13193; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Dcx; mouse.
DR PRO; PR:O88809; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; O88809; protein.
DR Bgee; ENSMUSG00000031285; Expressed in rostral migratory stream and 174 other tissues.
DR ExpressionAtlas; O88809; baseline and differential.
DR Genevisible; O88809; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005930; C:axoneme; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0048675; P:axon extension; IGI:MGI.
DR GO; GO:0035082; P:axoneme assembly; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IGI:MGI.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IGI:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IGI:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IGI:MGI.
DR GO; GO:0042461; P:photoreceptor cell development; IBA:GO_Central.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; ISO:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI.
DR GO; GO:0021860; P:pyramidal neuron development; IGI:MGI.
DR GO; GO:0060041; P:retina development in camera-type eye; IBA:GO_Central.
DR Gene3D; 3.10.20.230; -; 2.
DR InterPro; IPR017302; Doublecortin_chordata.
DR InterPro; IPR003533; Doublecortin_dom.
DR InterPro; IPR036572; Doublecortin_dom_sf.
DR InterPro; IPR040163; RP1/RP1L1/DCX.
DR PANTHER; PTHR23005; PTHR23005; 1.
DR Pfam; PF03607; DCX; 2.
DR PIRSF; PIRSF037870; Doublin; 1.
DR SMART; SM00537; DCX; 2.
DR SUPFAM; SSF89837; SSF89837; 2.
DR PROSITE; PS50309; DC; 2.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Developmental protein; Differentiation;
KW Microtubule; Neurogenesis; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..366
FT /note="Neuronal migration protein doublecortin"
FT /id="PRO_0000079834"
FT DOMAIN 53..139
FT /note="Doublecortin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072"
FT DOMAIN 180..263
FT /note="Doublecortin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072"
FT REGION 275..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191"
FT MOD_RES 47
FT /note="Phosphoserine; by MARK1 and PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9ESI7"
FT MOD_RES 70
FT /note="Phosphotyrosine; by ABL"
FT /evidence="ECO:0000255"
FT MOD_RES 74
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 90
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000255"
FT MOD_RES 110
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 115
FT /note="Phosphoserine; by CK2, MARK1 and PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9ESI7"
FT MOD_RES 265
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:22807455"
FT MOD_RES 287
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191"
FT MOD_RES 289
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191"
FT MOD_RES 294
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15099191,
FT ECO:0000269|PubMed:22807455"
FT MOD_RES 297
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191,
FT ECO:0000269|PubMed:22807455"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 326
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191"
FT MOD_RES 326
FT /note="Phosphothreonine; by PKC and MAPK"
FT /evidence="ECO:0000255"
FT MOD_RES 332
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 332
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000255"
FT MOD_RES 336
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000255"
FT MOD_RES 339
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:15099191,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 339
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000255"
FT MOD_RES 342
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 355
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000255"
FT MOD_RES 361
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000255"
FT MUTAGEN 28
FT /note="S->A: Reduces overall phosphorylation by 25%."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 287
FT /note="S->A: No effect on overall phosphorylation."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 289
FT /note="T->A: No effect on overall phosphorylation."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 297
FT /note="S->A: No effect on overall phosphorylation."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 326
FT /note="T->A: No effect on overall phosphorylation."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 332
FT /note="S->A: No effect on overall phosphorylation. Reduces
FT overall phosphorylation by 36%; when associated with A-
FT 339."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 336
FT /note="T->A: No effect on overall phosphorylation."
FT /evidence="ECO:0000269|PubMed:15099191"
FT MUTAGEN 339
FT /note="S->A: No effect on overall phosphorylation. Reduces
FT overall phosphorylation by 36%; when associated with A-
FT 332."
FT /evidence="ECO:0000269|PubMed:15099191"
FT CONFLICT 345
FT /note="K -> R (in Ref. 2; AAC31799)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="Missing (in Ref. 2; AAC31799)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 40613 MW; 323D0774C222F295 CRC64;
MELDFGHFDE RDKASRNMRG SRMNGLPSPT HSAHCSFYRT RTLQALSNEK KAKKVRFYRN
GDRYFKGIVY AVSSDRFRSF DALLADLTRS LSDNINLPQG VRYIYTIDGS RKIGSMDELE
EGESYVCSSD NFFKKVEYTK NVNPNWSVNV KTSANMKAPQ SLASSNSAQA RENKDFVRPK
LVTIIRSGVK PRKAVRVLLN KKTAHSFEQV LTDITEAIKL ETGVVKKLYT LDGKQVTCLH
DFFGDDDVFI ACGPEKFRYA QDDFSLDENE CRVMKGNPSA AAGPKASPTP QKTSAKSPGP
MRRSKSPADS GNDQDANGTS SSQLSTPKSK QSPISTPTSP GSLRKHKVDL YLPLSLDDSD
SLGDSM
