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   27-MAR-2024, entry version 185.
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   -!- INTERACTION:
CC       O88809; Q96M94: KLHL15; Xeno; NbExp=2; IntAct=EBI-16724620, EBI-2510129;
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}.
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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; 6.
DR   MINT; O88809; -.
DR   STRING; 10090.ENSMUSP00000033642; -.
DR   iPTMnet; O88809; -.
DR   PhosphoSitePlus; O88809; -.
DR   SwissPalm; O88809; -.
DR   PaxDb; 10090-ENSMUSP00000084570; -.
DR   PeptideAtlas; O88809; -.
DR   ProteomicsDB; 279319; -.
DR   Antibodypedia; 29535; 919 antibodies from 45 providers.
DR   DNASU; 13193; -.
DR   Ensembl; ENSMUST00000033642.10; ENSMUSP00000033642.4; ENSMUSG00000031285.15.
DR   Ensembl; ENSMUST00000087313.10; ENSMUSP00000084570.4; ENSMUSG00000031285.15.
DR   GeneID; 13193; -.
DR   KEGG; mmu:13193; -.
DR   UCSC; uc033jun.1; mouse.
DR   AGR; MGI:1277171; -.
DR   CTD; 1641; -.
DR   MGI; MGI:1277171; Dcx.
DR   VEuPathDB; HostDB:ENSMUSG00000031285; -.
DR   eggNOG; KOG3757; Eukaryota.
DR   GeneTree; ENSGT00940000161570; -.
DR   InParanoid; O88809; -.
DR   OrthoDB; 2956627at2759; -.
DR   PhylomeDB; O88809; -.
DR   TreeFam; TF318770; -.
DR   BioGRID-ORCS; 13193; 1 hit in 76 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 cell types or tissues.
DR   ExpressionAtlas; O88809; baseline and differential.
DR   GO; GO:0030424; C:axon; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0030426; C:growth cone; ISO:MGI.
DR   GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
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; IEA:InterPro.
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: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; IEA:InterPro.
DR   CDD; cd16112; DCX1_DCX; 1.
DR   CDD; cd17069; DCX2; 1.
DR   Gene3D; 3.10.20.230; Doublecortin domain; 2.
DR   InterPro; IPR049626; DCX/DCDC2-like.
DR   InterPro; IPR017302; DCX_chordates.
DR   InterPro; IPR003533; Doublecortin_dom.
DR   InterPro; IPR036572; Doublecortin_dom_sf.
DR   PANTHER; PTHR23004; DOUBLECORTIN DOMAIN CONTAINING 2; 1.
DR   PANTHER; PTHR23004:SF11; PROTEIN RPI-1; 1.
DR   Pfam; PF03607; DCX; 2.
DR   PIRSF; PIRSF037870; Doublin; 1.
DR   SMART; SM00537; DCX; 2.
DR   SUPFAM; SSF89837; Doublecortin (DC); 2.
DR   PROSITE; PS50309; DC; 2.
DR   Genevisible; O88809; MM.
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
FT                   A-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
FT                   A-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
//