{"gene":"DCX","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":2004,"finding":"DCX is a substrate of JNK (c-Jun N-terminal kinase) and physically interacts with both JNK and JNK interacting protein (JIP). DCX is phosphorylated by JNK specifically at growth cones. The localization of DCX at neurite tips is determined by its interaction with JIP and by JIP's interaction with kinesin. DCX mutated at JNK-phosphorylation sites affected neurite outgrowth and the velocity and relative pause time of migrating neurons.","method":"Kinase assay (JNK phosphorylation of DCX), co-immunoprecipitation (DCX-JNK and DCX-JIP interactions), site-directed mutagenesis of phosphorylation sites, live imaging of migrating neurons","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay with mutagenesis, co-IP, and live-cell functional readout in a single study","pmids":["14765123"],"is_preprint":false},{"year":2003,"finding":"The N-terminal DCX domain of human doublecortin adopts a ubiquitin-like tertiary fold with structural similarities to GTPase-binding domains. The N-terminal DCX domain binds only to assembled microtubules, whereas the C-terminal DCX domain binds to both assembled microtubules and unpolymerized tubulin. The C-terminal DCX domains of both doublecortin and DCLK are only partially folded.","method":"NMR solution structure (N-terminal DCX domain), 1.5 Å crystal structure (DCLK N-terminal DCX domain), in vitro microtubule/tubulin binding assays","journal":"Nature structural biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure, NMR structure, and functional binding assays in one study","pmids":["12692530"],"is_preprint":false},{"year":2006,"finding":"DCX is dephosphorylated at specific JNK-phosphorylated sites by protein phosphatase 1 (PP1), and this dephosphorylation is mediated by Neurabin II, which recruits PP1 to DCX. In vitro, PP1 dephosphorylates DCX site-specifically without Neurabin II, requiring an intact RVXF motif in DCX. Overexpression of the coiled-coil domain of Neurabin II (sufficient for DCX and endogenous Neurabin II/PP1 interaction) induced dephosphorylation of DCX at a JNK-phosphorylated site.","method":"In vitro phosphatase assay, co-immunoprecipitation (DCX-Neurabin II-PP1), site-directed mutagenesis (RVXF motif), overexpression in neurons with phospho-specific antibody readout","journal":"Molecular and cellular neurosciences","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro phosphatase assay with mutagenesis plus cellular co-IP and overexpression rescue in single study","pmids":["16530423"],"is_preprint":false},{"year":2010,"finding":"GSK3β phosphorylates DCX at Ser327, a site distinct from CDK5 and JNK sites, and this phosphorylation contributes to DCX function in restricting axon branching. JIP3 restricts axon branching by maintaining GSK3β levels; JIP3 knockdown downregulates GSK3β, and GSK3β knockdown phenocopies JIP3 knockdown. Thus DCX is a novel substrate of GSK3β in a JIP3-GSK3β-DCX signaling pathway that restricts axon branching.","method":"In vitro kinase assay (GSK3β phosphorylation of DCX at Ser327), RNAi knockdown in primary neurons and cerebellar slices and in vivo, epistasis analysis","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay identifying specific phosphorylation site, combined with in vivo epistasis and knockdown phenotype","pmids":["21159948"],"is_preprint":false},{"year":2012,"finding":"DCX promotes endocytosis of the cell adhesion molecule neurofascin from soma and dendrites, modulating its surface distribution in developing neurons. This endocytic adaptor function of DCX is independent of its microtubule-binding activity. The patient allele DCX-G253D retains microtubule binding but is deficient in promoting neurofascin endocytosis.","method":"Live-cell imaging and surface antibody feeding assays in cultured rat neurons, microtubule co-sedimentation assay, patient allele mutagenesis, co-immunoprecipitation","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — multiple orthogonal methods (endocytosis assay, MT binding, patient allele functional test) in single study","pmids":["22649224"],"is_preprint":false},{"year":2013,"finding":"DCX regulates filamentous actin (F-actin) structure in developing neurons. Loss of Dcx leads to increased F-actin around the cell body and decreased F-actin in neurites and growth cones. The C-terminal S/P-rich domain of DCX is required for this actin regulatory function, likely through interaction with spinophilin but not through α-actinin-4 or Arp3.","method":"Quantitative proteomics of corpus callosum from Dcx mutant mice, rescue experiments with full-length DCX and truncation/phospho-mutants, F-actin staining","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Moderate — proteomic analysis plus domain-mapping rescue experiments with specific mutants in neuronal cells","pmids":["23303949"],"is_preprint":false},{"year":2014,"finding":"Cdk5 phosphorylates DCX to regulate cytoplasmic dilation formation and nuclear elongation in migrating cortical neurons. Pharmacological or RNAi-mediated inhibition of Cdk5 suppresses both dilation formation and nuclear elongation; knockdown of Dcx (a Cdk5 substrate involved in microtubule organization and membrane/endocytic trafficking) similarly disrupts these migrating-neuron-specific features.","method":"Chemical inhibitor experiments ex vivo, RNAi knockdown of Cdk5 and Dcx in migrating neurons, live imaging of neuronal migration","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi knockdown with specific phenotypic readout and epistasis; kinase-substrate relationship inferred from prior literature rather than demonstrated by in vitro assay in this paper","pmids":["25183872"],"is_preprint":false},{"year":2008,"finding":"RNAi knockdown of DCX or LIS1 in vivo disrupts neuronal migration along the lateral cortical stream (LCS) into the amygdala and piriform cortex. Combinatorial RNAi of both LIS1 and DCX further suggests a functional interaction between these proteins in migrating neurons in the LCS, affecting neuron morphology and migration.","method":"In utero electroporation with RNAi in mice, combinatorial knockdown epistasis analysis, histological readout of migration","journal":"Developmental neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo RNAi with epistasis analysis; no biochemical reconstitution of the interaction","pmids":["18075262"],"is_preprint":false},{"year":2001,"finding":"DCX overexpression in PC12 cells stabilizes microtubules and inhibits neurite outgrowth under NGF-induced differentiation, but increases neurite length under EGF/forskolin or dibutyryl-cAMP treatment. DCX overexpression downregulates CREB-mediated transcription. A lissencephaly patient mutation (S47R) completely blocks neurite outgrowth. Microtubule stabilization is a key but not sole factor controlling neurite extension by DCX.","method":"Overexpression in PC12 cells, patient allele mutagenesis, microtubule stabilization assays, neurite outgrowth quantification, CREB reporter assays","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function plus patient allele mutagenesis with defined cellular readouts; single lab study","pmids":["11331616"],"is_preprint":false},{"year":2006,"finding":"DCX domain proteins as a superfamily share conserved roles in microtubule regulation: all tested DCX-domain proteins stimulate microtubule assembly in vitro. Proteins with tandem DCX repeats stabilize the microtubule cytoskeleton in transfected cells, while those with single repeats localize to actin-rich structures or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subset interacted with Neurabin 2, and a non-overlapping group showed actin association.","method":"In vitro microtubule assembly assay, transfection with immunofluorescence, co-immunoprecipitation","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro assembly assay and Co-IP for multiple family members; findings specific to canonical DCX confirmed but embedded in superfamily analysis","pmids":["16628014"],"is_preprint":false},{"year":2017,"finding":"Using iPSC-derived neural stem cells from DCX-mutant lissencephaly patients, absent or reduced DCX protein expression causes impaired migration, delayed differentiation, and deficient neurite formation, expanding the role of DCX beyond microtubule stabilization to include neuronal differentiation and neurite outgrowth.","method":"iPSC disease modeling, neural differentiation assays, expression profiling, migration assays in patient-derived cells","journal":"Molecular psychiatry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient-derived iPSC model with defined phenotypic readouts; single lab, no biochemical reconstitution","pmids":["28924182"],"is_preprint":false},{"year":1998,"finding":"Loss-of-function mutations in DCX (XLIS) cause X-linked lissencephaly in hemizygous males and subcortical band heterotopia in heterozygous carrier females, establishing DCX as required for normal neuronal migration. Point mutations in the C-terminal serine/proline-rich region identify this region as important for DCX function.","method":"Direct DNA sequencing of patients, genotype-phenotype correlation in LIS/SBH pedigrees","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Strong — genetic loss-of-function with defined brain malformation phenotype replicated across multiple studies; no biochemical mechanism established in this paper","pmids":["9817918"],"is_preprint":false},{"year":1998,"finding":"Doublecortin (DCX) is exclusively expressed in fetal brain and adult frontal lobe, encodes isoforms of a highly hydrophilic ~40 kDa protein with several potential phosphorylation sites, and is homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting DCX may function through Ca2+-dependent signaling. Mutations cause LIS/SBH.","method":"Gene cloning, Northern blot, protein sequence analysis, patient mutation identification","journal":"Human molecular genetics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence-based prediction of Ca2+-dependent signaling; no direct biochemical demonstration","pmids":["9668176"],"is_preprint":false}],"current_model":"DCX (doublecortin) is a microtubule-associated protein expressed in migrating neurons that stabilizes microtubules via tandem DCX domains (N-terminal domain binds assembled microtubules; C-terminal domain binds both tubulin and microtubules), acts as an endocytic adaptor for neurofascin independently of microtubule binding, and functions as a signaling hub phosphorylated by JNK (at growth cones, scaffolded by JIP/kinesin), GSK3β (Ser327, restricting axon branching downstream of JIP3), and Cdk5, with site-specific dephosphorylation mediated by PP1 recruited via Neurabin II; its C-terminal S/P-rich domain additionally regulates F-actin distribution in neurites, and loss-of-function mutations cause lissencephaly and subcortical band heterotopia due to impaired neuronal migration, differentiation, and neurite formation."},"narrative":{"mechanistic_narrative":"DCX (doublecortin) is a neuronal microtubule-associated protein required for cortical neuronal migration, whose loss-of-function mutations cause X-linked lissencephaly in males and subcortical band heterotopia in carrier females [PMID:9817918]. Its structural basis lies in tandem DCX domains: the N-terminal domain adopts a ubiquitin-like fold and binds only assembled microtubules, while the partially folded C-terminal domain binds both microtubules and unpolymerized tubulin, enabling DCX to stimulate microtubule assembly and stabilize the cytoskeleton [PMID:12692530, PMID:16628014]. Beyond microtubule stabilization, DCX serves as an endocytic adaptor that promotes internalization of the cell adhesion molecule neurofascin independently of microtubule binding, and it shapes F-actin distribution in neurites through its C-terminal serine/proline-rich domain via spinophilin [PMID:22649224, PMID:23303949]. DCX integrates multiple signaling inputs as a phosphorylation hub: JNK phosphorylates DCX at growth cones with its localization set by JIP/kinesin, GSK3β phosphorylates Ser327 downstream of JIP3 to restrict axon branching, and Cdk5 regulates dilation formation and nuclear elongation in migrating neurons, with PP1 reversing JNK-site phosphorylation through Neurabin II recruitment [PMID:14765123, PMID:16530423, PMID:21159948, PMID:25183872]. Functionally, DCX cooperates with LIS1 in migrating neurons and is required not only for migration but also for neuronal differentiation and neurite formation [PMID:18075262, PMID:28924182].","teleology":[{"year":1998,"claim":"Establishing that DCX is genetically required for neuronal migration defined the disease relevance and the core biological process the protein serves.","evidence":"DNA sequencing and genotype-phenotype correlation in lissencephaly/SBH pedigrees, plus gene cloning and expression profiling","pmids":["9817918","9668176"],"confidence":"Medium","gaps":["No biochemical mechanism established","C-terminal S/P-rich region implicated by mutation but its molecular role undefined"]},{"year":2001,"claim":"Linking DCX overexpression to microtubule stabilization and altered neurite outgrowth began to connect its molecular activity to a cellular phenotype, while a patient allele showed migration biology is not purely microtubule-based.","evidence":"Overexpression and patient-allele mutagenesis in PC12 cells with microtubule and neurite-outgrowth readouts and CREB reporter assays","pmids":["11331616"],"confidence":"Medium","gaps":["Single cell-line gain-of-function system","Microtubule stabilization stated to be 'not sole factor' without identifying the others"]},{"year":2003,"claim":"Solving the tandem DCX domain structures revealed the molecular basis for differential tubulin and microtubule binding, explaining how DCX engages the cytoskeleton.","evidence":"NMR and crystal structures of N-terminal domains plus in vitro microtubule/tubulin binding assays","pmids":["12692530"],"confidence":"High","gaps":["C-terminal domain only partially folded and structurally unresolved","Does not show how binding is regulated in cells"]},{"year":2004,"claim":"Identifying DCX as a JNK substrate scaffolded by JIP/kinesin placed it within a signaling and transport framework controlling its localization and migration function.","evidence":"In vitro kinase assay, co-IP, phospho-site mutagenesis, and live imaging of migrating neurons","pmids":["14765123"],"confidence":"High","gaps":["Functional consequence of individual phospho-sites on microtubule binding not resolved","How JNK signaling is spatially triggered at growth cones unclear"]},{"year":2006,"claim":"Demonstrating PP1/Neurabin II-mediated dephosphorylation and superfamily-wide microtubule activity established that DCX phosphorylation is dynamically reversible and that its cytoskeletal role is shared across DCX-domain proteins.","evidence":"In vitro phosphatase assay with RVXF-motif mutagenesis, co-IP, and in vitro microtubule assembly assays across family members","pmids":["16530423","16628014"],"confidence":"High","gaps":["Functional impact of the PP1/JNK phospho-cycle on migration not directly tested","Which kinase-phosphatase pairs operate at which subcellular sites unknown"]},{"year":2008,"claim":"Showing a functional interaction between DCX and LIS1 in vivo connected DCX to a broader migration machinery.","evidence":"In utero electroporation RNAi with combinatorial knockdown epistasis and histological migration readout","pmids":["18075262"],"confidence":"Medium","gaps":["No biochemical reconstitution of the DCX-LIS1 interaction","Mechanism of cooperativity unresolved"]},{"year":2010,"claim":"Placing DCX in a JIP3-GSK3β pathway that phosphorylates Ser327 defined a discrete signaling axis restricting axon branching, distinct from JNK and Cdk5 inputs.","evidence":"In vitro kinase assay mapping Ser327 plus RNAi knockdown and epistasis in primary neurons, slices, and in vivo","pmids":["21159948"],"confidence":"High","gaps":["Downstream effector of Ser327 phosphorylation not identified","Whether Ser327 alters microtubule or actin binding unknown"]},{"year":2012,"claim":"Discovering a microtubule-independent endocytic adaptor function for neurofascin expanded DCX beyond a cytoskeletal protein and explained a patient allele that retains microtubule binding yet causes disease.","evidence":"Live-cell surface-feeding endocytosis assays, microtubule co-sedimentation, patient-allele (G253D) mutagenesis, and co-IP in cultured neurons","pmids":["22649224"],"confidence":"High","gaps":["Endocytic machinery partners DCX recruits are unidentified","Relative contribution of endocytic vs microtubule function to migration not quantified"]},{"year":2013,"claim":"Mapping F-actin regulation to the C-terminal S/P-rich domain via spinophilin identified a second cytoskeletal axis controlled by DCX.","evidence":"Quantitative proteomics of Dcx-mutant corpus callosum with domain/phospho-mutant rescue and F-actin staining","pmids":["23303949"],"confidence":"High","gaps":["Direct DCX-spinophilin interaction mechanism not fully resolved","α-actinin-4 and Arp3 excluded but the actin effector chain incomplete"]},{"year":2014,"claim":"Linking Cdk5-dependent DCX phosphorylation to cytoplasmic dilation and nuclear elongation tied DCX phospho-regulation to migration-specific cell-shape changes.","evidence":"Chemical inhibition and RNAi of Cdk5 and Dcx with live imaging of migrating neurons","pmids":["25183872"],"confidence":"Medium","gaps":["Cdk5-DCX kinase-substrate relationship inferred rather than shown by in vitro assay in this study","Specific Cdk5 phospho-sites driving the phenotype not mapped"]},{"year":2017,"claim":"Patient iPSC-derived neural stem cell modeling demonstrated DCX is required for neuronal differentiation and neurite formation, broadening its role beyond migration.","evidence":"iPSC disease modeling with neural differentiation, expression profiling, and migration assays in patient-derived cells","pmids":["28924182"],"confidence":"Medium","gaps":["Molecular pathway linking DCX loss to differentiation delay not defined","Single-lab model without biochemical reconstitution"]},{"year":null,"claim":"How DCX's distinct activities — microtubule stabilization, actin regulation, and neurofascin endocytosis — are coordinated by its phosphorylation state at a given subcellular site to drive migration remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated model connecting specific phospho-sites to each functional output","Spatial-temporal switching between cytoskeletal and adaptor roles uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,8,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2,3]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,5]}],"pathway":[{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[7,10,11]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[4]}],"complexes":[],"partners":["JNK","JIP","JIP3","GSK3B","PPP1CA","PPP1R9B","NFASC","LIS1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43602","full_name":"Neuronal migration protein doublecortin","aliases":["Doublin","Lissencephalin-X","Lis-X"],"length_aa":365,"mass_kda":40.6,"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","subcellular_location":"Cytoplasm; Cell projection, neuron projection","url":"https://www.uniprot.org/uniprotkb/O43602/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DCX","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DCX","total_profiled":1310},"omim":[{"mim_id":"618873","title":"LISSENCEPHALY 10; LIS10","url":"https://www.omim.org/entry/618873"},{"mim_id":"618865","title":"CEP85-LIKE PROTEIN; CEP85L","url":"https://www.omim.org/entry/618865"},{"mim_id":"613167","title":"DOUBLECORTIN-LIKE KINASE 3; DCLK3","url":"https://www.omim.org/entry/613167"},{"mim_id":"613166","title":"DOUBLECORTIN-LIKE KINASE 2; DCLK2","url":"https://www.omim.org/entry/613166"},{"mim_id":"611603","title":"LISSENCEPHALY 3; LIS3","url":"https://www.omim.org/entry/611603"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":5.8},{"tissue":"retina","ntpm":2.0}],"url":"https://www.proteinatlas.org/search/DCX"},"hgnc":{"alias_symbol":["SCLH","DC","LISX","DBCN","XLIS"],"prev_symbol":[]},"alphafold":{"accession":"O43602","domains":[{"cath_id":"3.10.20.230","chopping":"50-146","consensus_level":"high","plddt":87.3223,"start":50,"end":146},{"cath_id":"3.10.20.230","chopping":"178-273","consensus_level":"high","plddt":76.9747,"start":178,"end":273}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43602","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43602-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43602-F1-predicted_aligned_error_v6.png","plddt_mean":66.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DCX","jax_strain_url":"https://www.jax.org/strain/search?query=DCX"},"sequence":{"accession":"O43602","fasta_url":"https://rest.uniprot.org/uniprotkb/O43602.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43602/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43602"}},"corpus_meta":[{"pmid":"12949494","id":"PMC_12949494","title":"DC-SIGN: escape mechanism for pathogens.","date":"2003","source":"Nature reviews. Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12949494","citation_count":698,"is_preprint":false},{"pmid":"11739956","id":"PMC_11739956","title":"Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR.","date":"2001","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/11739956","citation_count":553,"is_preprint":false},{"pmid":"15195147","id":"PMC_15195147","title":"Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR.","date":"2004","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15195147","citation_count":477,"is_preprint":false},{"pmid":"17476349","id":"PMC_17476349","title":"DC-based cancer vaccines.","date":"2007","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/17476349","citation_count":467,"is_preprint":false},{"pmid":"12672047","id":"PMC_12672047","title":"Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines.","date":"2003","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12672047","citation_count":411,"is_preprint":false},{"pmid":"14698284","id":"PMC_14698284","title":"NK cell and DC interactions.","date":"2004","source":"Trends in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/14698284","citation_count":352,"is_preprint":false},{"pmid":"12504546","id":"PMC_12504546","title":"DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells.","date":"2003","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/12504546","citation_count":299,"is_preprint":false},{"pmid":"12634366","id":"PMC_12634366","title":"Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR.","date":"2003","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12634366","citation_count":294,"is_preprint":false},{"pmid":"15452179","id":"PMC_15452179","title":"RANKL-induced DC-STAMP is essential for osteoclastogenesis.","date":"2004","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/15452179","citation_count":285,"is_preprint":false},{"pmid":"16415006","id":"PMC_16415006","title":"West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection.","date":"2006","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/16415006","citation_count":281,"is_preprint":false},{"pmid":"9817918","id":"PMC_9817918","title":"LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation.","date":"1998","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9817918","citation_count":278,"is_preprint":false},{"pmid":"9618162","id":"PMC_9618162","title":"doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH).","date":"1998","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9618162","citation_count":215,"is_preprint":false},{"pmid":"10975799","id":"PMC_10975799","title":"DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13.","date":"2000","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/10975799","citation_count":215,"is_preprint":false},{"pmid":"21767814","id":"PMC_21767814","title":"DC-SIGN as a receptor for phleboviruses.","date":"2011","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/21767814","citation_count":194,"is_preprint":false},{"pmid":"11102169","id":"PMC_11102169","title":"Absence of dc-conductivity in lambda-DNA.","date":"2000","source":"Physical review letters","url":"https://pubmed.ncbi.nlm.nih.gov/11102169","citation_count":189,"is_preprint":false},{"pmid":"14765123","id":"PMC_14765123","title":"DCX, a new mediator of the JNK pathway.","date":"2004","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/14765123","citation_count":182,"is_preprint":false},{"pmid":"20124100","id":"PMC_20124100","title":"Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function.","date":"2010","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/20124100","citation_count":181,"is_preprint":false},{"pmid":"15509576","id":"PMC_15509576","title":"Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15509576","citation_count":154,"is_preprint":false},{"pmid":"19713529","id":"PMC_19713529","title":"MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness.","date":"2009","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/19713529","citation_count":137,"is_preprint":false},{"pmid":"17964853","id":"PMC_17964853","title":"DC ablation in mice: promises, pitfalls, and challenges.","date":"2007","source":"Trends in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17964853","citation_count":129,"is_preprint":false},{"pmid":"33255895","id":"PMC_33255895","title":"DC-Based Vaccines for Cancer Immunotherapy.","date":"2020","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/33255895","citation_count":122,"is_preprint":false},{"pmid":"16978536","id":"PMC_16978536","title":"DC-SIGN and immunoregulation.","date":"2006","source":"Cellular & molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16978536","citation_count":119,"is_preprint":false},{"pmid":"19137537","id":"PMC_19137537","title":"Phenotype and function of neonatal DC.","date":"2009","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19137537","citation_count":117,"is_preprint":false},{"pmid":"11175293","id":"PMC_11175293","title":"Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.","date":"2001","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/11175293","citation_count":116,"is_preprint":false},{"pmid":"12692530","id":"PMC_12692530","title":"The DCX-domain tandems of doublecortin and doublecortin-like kinase.","date":"2003","source":"Nature structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/12692530","citation_count":112,"is_preprint":false},{"pmid":"18832334","id":"PMC_18832334","title":"DCX and PSA-NCAM expression identifies a population of neurons preferentially distributed in associative areas of different pallial derivatives and vertebrate species.","date":"2008","source":"Cerebral cortex (New York, N.Y. : 1991)","url":"https://pubmed.ncbi.nlm.nih.gov/18832334","citation_count":108,"is_preprint":false},{"pmid":"10441340","id":"PMC_10441340","title":"Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.","date":"1999","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10441340","citation_count":103,"is_preprint":false},{"pmid":"12974773","id":"PMC_12974773","title":"Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity.","date":"2003","source":"APMIS : acta pathologica, microbiologica, et immunologica Scandinavica","url":"https://pubmed.ncbi.nlm.nih.gov/12974773","citation_count":98,"is_preprint":false},{"pmid":"16869982","id":"PMC_16869982","title":"The evolving doublecortin (DCX) superfamily.","date":"2006","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/16869982","citation_count":97,"is_preprint":false},{"pmid":"34359569","id":"PMC_34359569","title":"DC-Derived Exosomes for Cancer Immunotherapy.","date":"2021","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/34359569","citation_count":93,"is_preprint":false},{"pmid":"27018136","id":"PMC_27018136","title":"DC-STAMP: A Key Regulator in Osteoclast Differentiation.","date":"2016","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/27018136","citation_count":84,"is_preprint":false},{"pmid":"20039274","id":"PMC_20039274","title":"RANKL induces heterogeneous DC-STAMP(lo) and DC-STAMP(hi) osteoclast precursors of which the DC-STAMP(lo) precursors are the master fusogens.","date":"2010","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/20039274","citation_count":83,"is_preprint":false},{"pmid":"9668176","id":"PMC_9668176","title":"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.","date":"1998","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9668176","citation_count":80,"is_preprint":false},{"pmid":"9097958","id":"PMC_9097958","title":"Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain.","date":"1997","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9097958","citation_count":79,"is_preprint":false},{"pmid":"18534908","id":"PMC_18534908","title":"Turning NF-kappaB and IRFs on and off in DC.","date":"2008","source":"Trends in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18534908","citation_count":79,"is_preprint":false},{"pmid":"19722841","id":"PMC_19722841","title":"Pathogen recognition by DC-SIGN shapes adaptive immunity.","date":"2009","source":"Future microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19722841","citation_count":78,"is_preprint":false},{"pmid":"16816373","id":"PMC_16816373","title":"Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles.","date":"2006","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/16816373","citation_count":78,"is_preprint":false},{"pmid":"33345899","id":"PMC_33345899","title":"Antibacterial properties and mechanism of selenium nanoparticles synthesized by Providencia sp. DCX.","date":"2020","source":"Environmental research","url":"https://pubmed.ncbi.nlm.nih.gov/33345899","citation_count":75,"is_preprint":false},{"pmid":"18664532","id":"PMC_18664532","title":"Human dendritic cell line models for DC differentiation and clinical DC vaccination studies.","date":"2008","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/18664532","citation_count":74,"is_preprint":false},{"pmid":"12653690","id":"PMC_12653690","title":"DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe?","date":"2003","source":"Clinical science (London, England : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/12653690","citation_count":71,"is_preprint":false},{"pmid":"6946426","id":"PMC_6946426","title":"7-Methylguanine in poly(dG-dC).poly(dG-dC) facilitates z-DNA formation.","date":"1981","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/6946426","citation_count":71,"is_preprint":false},{"pmid":"19221293","id":"PMC_19221293","title":"NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children.","date":"2009","source":"Neurology","url":"https://pubmed.ncbi.nlm.nih.gov/19221293","citation_count":70,"is_preprint":false},{"pmid":"24487587","id":"PMC_24487587","title":"Hyaluronan digestion controls DC migration from the skin.","date":"2014","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/24487587","citation_count":69,"is_preprint":false},{"pmid":"22013110","id":"PMC_22013110","title":"Semen clusterin is a novel DC-SIGN ligand.","date":"2011","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/22013110","citation_count":61,"is_preprint":false},{"pmid":"18083206","id":"PMC_18083206","title":"Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding.","date":"2008","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/18083206","citation_count":60,"is_preprint":false},{"pmid":"16420576","id":"PMC_16420576","title":"Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes.","date":"2006","source":"Journal of thrombosis and haemostasis : JTH","url":"https://pubmed.ncbi.nlm.nih.gov/16420576","citation_count":59,"is_preprint":false},{"pmid":"16628014","id":"PMC_16628014","title":"Common and divergent roles for members of the mouse DCX superfamily.","date":"2006","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/16628014","citation_count":59,"is_preprint":false},{"pmid":"23303949","id":"PMC_23303949","title":"Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons.","date":"2013","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/23303949","citation_count":57,"is_preprint":false},{"pmid":"24156700","id":"PMC_24156700","title":"DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection.","date":"2013","source":"International reviews of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/24156700","citation_count":56,"is_preprint":false},{"pmid":"28097157","id":"PMC_28097157","title":"NK-DC Crosstalk in Immunity to Microbial Infection.","date":"2016","source":"Journal of immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/28097157","citation_count":55,"is_preprint":false},{"pmid":"28539427","id":"PMC_28539427","title":"TLR-Induced Murine Dendritic Cell (DC) Activation Requires DC-Intrinsic Complement.","date":"2017","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/28539427","citation_count":53,"is_preprint":false},{"pmid":"21159948","id":"PMC_21159948","title":"A JIP3-regulated GSK3β/DCX signaling pathway restricts axon branching.","date":"2010","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21159948","citation_count":50,"is_preprint":false},{"pmid":"19050731","id":"PMC_19050731","title":"Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia.","date":"2008","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/19050731","citation_count":50,"is_preprint":false},{"pmid":"23369527","id":"PMC_23369527","title":"Human tolerogenic DC-10: perspectives for clinical applications.","date":"2012","source":"Transplantation research","url":"https://pubmed.ncbi.nlm.nih.gov/23369527","citation_count":50,"is_preprint":false},{"pmid":"18230156","id":"PMC_18230156","title":"Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression.","date":"2008","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/18230156","citation_count":49,"is_preprint":false},{"pmid":"36303448","id":"PMC_36303448","title":"Guidelines for mouse and human DC generation.","date":"2022","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36303448","citation_count":48,"is_preprint":false},{"pmid":"31270240","id":"PMC_31270240","title":"Antigen structure affects cellular routing through DC-SIGN.","date":"2019","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31270240","citation_count":48,"is_preprint":false},{"pmid":"25183872","id":"PMC_25183872","title":"Cdk5 and its substrates, Dcx and p27kip1, regulate cytoplasmic dilation formation and nuclear elongation in migrating neurons.","date":"2014","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/25183872","citation_count":47,"is_preprint":false},{"pmid":"22002016","id":"PMC_22002016","title":"CISH is induced during DC development and regulates DC-mediated CTL activation.","date":"2011","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/22002016","citation_count":45,"is_preprint":false},{"pmid":"17786606","id":"PMC_17786606","title":"MSC-DC interactions: MSC inhibit maturation and migration of BM-derived DC.","date":"2007","source":"Cytotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/17786606","citation_count":45,"is_preprint":false},{"pmid":"22747463","id":"PMC_22747463","title":"Noncarbohydrate glycomimetics and glycoprotein surrogates as DC-SIGN antagonists and agonists.","date":"2012","source":"ACS chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/22747463","citation_count":44,"is_preprint":false},{"pmid":"28924182","id":"PMC_28924182","title":"An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis.","date":"2017","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/28924182","citation_count":44,"is_preprint":false},{"pmid":"24463034","id":"PMC_24463034","title":"Medicinal properties and conservation of Pelargonium sidoides DC.","date":"2014","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/24463034","citation_count":44,"is_preprint":false},{"pmid":"18075262","id":"PMC_18075262","title":"The role of DCX and LIS1 in migration through the lateral cortical stream of developing forebrain.","date":"2008","source":"Developmental neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/18075262","citation_count":42,"is_preprint":false},{"pmid":"22649224","id":"PMC_22649224","title":"Doublecortin (DCX) mediates endocytosis of neurofascin independently of microtubule binding.","date":"2012","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22649224","citation_count":40,"is_preprint":false},{"pmid":"25504222","id":"PMC_25504222","title":"The clinical significance of DC-SIGN and DC-SIGNR, which are novel markers expressed in human colon cancer.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25504222","citation_count":39,"is_preprint":false},{"pmid":"15614772","id":"PMC_15614772","title":"Expression of doublecortin (DCX) and doublecortin-like kinase (DCLK) within the developing chick brain.","date":"2005","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/15614772","citation_count":38,"is_preprint":false},{"pmid":"16530423","id":"PMC_16530423","title":"Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1).","date":"2006","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/16530423","citation_count":37,"is_preprint":false},{"pmid":"24623090","id":"PMC_24623090","title":"Distinct usage of three C-type lectins by Japanese encephalitis virus: DC-SIGN, DC-SIGNR, and LSECtin.","date":"2014","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/24623090","citation_count":37,"is_preprint":false},{"pmid":"10051403","id":"PMC_10051403","title":"Genomic structure, chromosomal mapping, and expression pattern of human DCAMKL1 (KIAA0369), a homologue of DCX (XLIS).","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10051403","citation_count":35,"is_preprint":false},{"pmid":"16569675","id":"PMC_16569675","title":"Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN.","date":"2006","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16569675","citation_count":35,"is_preprint":false},{"pmid":"10449167","id":"PMC_10449167","title":"Immunobiology of DC in NOD mice.","date":"1999","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/10449167","citation_count":34,"is_preprint":false},{"pmid":"27932494","id":"PMC_27932494","title":"Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/27932494","citation_count":34,"is_preprint":false},{"pmid":"11331616","id":"PMC_11331616","title":"DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth.","date":"2001","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11331616","citation_count":33,"is_preprint":false},{"pmid":"18685874","id":"PMC_18685874","title":"The location of DCX mutations predicts malformation severity in X-linked lissencephaly.","date":"2008","source":"Neurogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/18685874","citation_count":32,"is_preprint":false},{"pmid":"27734954","id":"PMC_27734954","title":"Pseudo-Mannosylated DC-SIGN Ligands as Immunomodulants.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27734954","citation_count":31,"is_preprint":false},{"pmid":"21152451","id":"PMC_21152451","title":"Targeting DC-SIGN with carbohydrate multivalent systems.","date":"2010","source":"Drug news & perspectives","url":"https://pubmed.ncbi.nlm.nih.gov/21152451","citation_count":31,"is_preprint":false},{"pmid":"28199142","id":"PMC_28199142","title":"DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption.","date":"2017","source":"Journal of dental research","url":"https://pubmed.ncbi.nlm.nih.gov/28199142","citation_count":31,"is_preprint":false},{"pmid":"29752722","id":"PMC_29752722","title":"A new cancer immunotherapy via simultaneous DC-mobilization and DC-targeted IDO gene silencing using an immune-stimulatory nanosystem.","date":"2018","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29752722","citation_count":31,"is_preprint":false},{"pmid":"19544312","id":"PMC_19544312","title":"Type I IFN regulate DC turnover in vivo.","date":"2009","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19544312","citation_count":31,"is_preprint":false},{"pmid":"23690918","id":"PMC_23690918","title":"Analysis of adult neurogenesis: evidence for a prominent \"non-neurogenic\" DCX-protein pool in rodent brain.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23690918","citation_count":30,"is_preprint":false},{"pmid":"16814268","id":"PMC_16814268","title":"The distribution of expression of doublecortin (DCX) mRNA and protein in the zebra finch brain.","date":"2006","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/16814268","citation_count":29,"is_preprint":false},{"pmid":"12957386","id":"PMC_12957386","title":"Isolation and characterization of the human DC-SIGN and DC-SIGNR promoters.","date":"2003","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/12957386","citation_count":28,"is_preprint":false},{"pmid":"20813757","id":"PMC_20813757","title":"Chemical discrimination between dC and 5MedC via their hydroxylamine adducts.","date":"2010","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/20813757","citation_count":28,"is_preprint":false},{"pmid":"19941104","id":"PMC_19941104","title":"Isolation of human blood DC subtypes.","date":"2010","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/19941104","citation_count":28,"is_preprint":false},{"pmid":"30443988","id":"PMC_30443988","title":"Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease.","date":"2018","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30443988","citation_count":26,"is_preprint":false},{"pmid":"15118415","id":"PMC_15118415","title":"DCX's phosphorylation by not just another kinase (JNK).","date":"2004","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/15118415","citation_count":26,"is_preprint":false},{"pmid":"19249311","id":"PMC_19249311","title":"Autonomous tetramerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19249311","citation_count":26,"is_preprint":false},{"pmid":"15057976","id":"PMC_15057976","title":"Neocortical neuronal arrangement in LIS1 and DCX lissencephaly may be different.","date":"2004","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/15057976","citation_count":25,"is_preprint":false},{"pmid":"19941313","id":"PMC_19941313","title":"DC expressing transgene Foxp3 are regulatory APC.","date":"2010","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19941313","citation_count":23,"is_preprint":false},{"pmid":"18231966","id":"PMC_18231966","title":"Doublecortin (DCX) and doublecortin-like (DCL) are differentially expressed in the early but not late stages of murine neocortical development.","date":"2008","source":"The Journal of comparative neurology","url":"https://pubmed.ncbi.nlm.nih.gov/18231966","citation_count":23,"is_preprint":false},{"pmid":"31840058","id":"PMC_31840058","title":"Epigenetic stabilization of DC and DC precursor classical activation by TNFα contributes to protective T cell polarization.","date":"2019","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/31840058","citation_count":23,"is_preprint":false},{"pmid":"26082689","id":"PMC_26082689","title":"Increased doublecortin (DCX) expression and incidence of DCX-immunoreactive multipolar cells in the subventricular zone-olfactory bulb system of suicides.","date":"2015","source":"Frontiers in neuroanatomy","url":"https://pubmed.ncbi.nlm.nih.gov/26082689","citation_count":22,"is_preprint":false},{"pmid":"17135574","id":"PMC_17135574","title":"Relevance of DC-SIGN in DC-induced T cell proliferation.","date":"2006","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/17135574","citation_count":22,"is_preprint":false},{"pmid":"26683148","id":"PMC_26683148","title":"SLE-associated risk factors affect DC function.","date":"2016","source":"Immunological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/26683148","citation_count":21,"is_preprint":false},{"pmid":"17660953","id":"PMC_17660953","title":"Selection of DNA aptamers against DC-SIGN protein.","date":"2007","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17660953","citation_count":21,"is_preprint":false},{"pmid":"22408144","id":"PMC_22408144","title":"Lissencephaly and band heterotopia: LIS1, TUBA1A, and DCX mutations in Hungary.","date":"2012","source":"Journal of child neurology","url":"https://pubmed.ncbi.nlm.nih.gov/22408144","citation_count":21,"is_preprint":false},{"pmid":"33208869","id":"PMC_33208869","title":"DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33208869","citation_count":21,"is_preprint":false},{"pmid":"33743782","id":"PMC_33743782","title":"Epigenetic evidence of an Ac/Dc axis by VPA and SAHA.","date":"2021","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/33743782","citation_count":20,"is_preprint":false},{"pmid":"18040806","id":"PMC_18040806","title":"Methamphetamine modulates DC-SIGN expression by mature dendritic cells.","date":"2006","source":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/18040806","citation_count":20,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":44523,"output_tokens":3590,"usd":0.09371,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11240,"output_tokens":3564,"usd":0.07265,"stage2_stop_reason":"end_turn"},"total_usd":0.16636,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"DCX is a substrate of JNK (c-Jun N-terminal kinase) and physically interacts with both JNK and JNK interacting protein (JIP). DCX is phosphorylated by JNK specifically at growth cones. The localization of DCX at neurite tips is determined by its interaction with JIP and by JIP's interaction with kinesin. DCX mutated at JNK-phosphorylation sites affected neurite outgrowth and the velocity and relative pause time of migrating neurons.\",\n      \"method\": \"Kinase assay (JNK phosphorylation of DCX), co-immunoprecipitation (DCX-JNK and DCX-JIP interactions), site-directed mutagenesis of phosphorylation sites, live imaging of migrating neurons\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay with mutagenesis, co-IP, and live-cell functional readout in a single study\",\n      \"pmids\": [\"14765123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The N-terminal DCX domain of human doublecortin adopts a ubiquitin-like tertiary fold with structural similarities to GTPase-binding domains. The N-terminal DCX domain binds only to assembled microtubules, whereas the C-terminal DCX domain binds to both assembled microtubules and unpolymerized tubulin. The C-terminal DCX domains of both doublecortin and DCLK are only partially folded.\",\n      \"method\": \"NMR solution structure (N-terminal DCX domain), 1.5 Å crystal structure (DCLK N-terminal DCX domain), in vitro microtubule/tubulin binding assays\",\n      \"journal\": \"Nature structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure, NMR structure, and functional binding assays in one study\",\n      \"pmids\": [\"12692530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"DCX is dephosphorylated at specific JNK-phosphorylated sites by protein phosphatase 1 (PP1), and this dephosphorylation is mediated by Neurabin II, which recruits PP1 to DCX. In vitro, PP1 dephosphorylates DCX site-specifically without Neurabin II, requiring an intact RVXF motif in DCX. Overexpression of the coiled-coil domain of Neurabin II (sufficient for DCX and endogenous Neurabin II/PP1 interaction) induced dephosphorylation of DCX at a JNK-phosphorylated site.\",\n      \"method\": \"In vitro phosphatase assay, co-immunoprecipitation (DCX-Neurabin II-PP1), site-directed mutagenesis (RVXF motif), overexpression in neurons with phospho-specific antibody readout\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro phosphatase assay with mutagenesis plus cellular co-IP and overexpression rescue in single study\",\n      \"pmids\": [\"16530423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"GSK3β phosphorylates DCX at Ser327, a site distinct from CDK5 and JNK sites, and this phosphorylation contributes to DCX function in restricting axon branching. JIP3 restricts axon branching by maintaining GSK3β levels; JIP3 knockdown downregulates GSK3β, and GSK3β knockdown phenocopies JIP3 knockdown. Thus DCX is a novel substrate of GSK3β in a JIP3-GSK3β-DCX signaling pathway that restricts axon branching.\",\n      \"method\": \"In vitro kinase assay (GSK3β phosphorylation of DCX at Ser327), RNAi knockdown in primary neurons and cerebellar slices and in vivo, epistasis analysis\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay identifying specific phosphorylation site, combined with in vivo epistasis and knockdown phenotype\",\n      \"pmids\": [\"21159948\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"DCX promotes endocytosis of the cell adhesion molecule neurofascin from soma and dendrites, modulating its surface distribution in developing neurons. This endocytic adaptor function of DCX is independent of its microtubule-binding activity. The patient allele DCX-G253D retains microtubule binding but is deficient in promoting neurofascin endocytosis.\",\n      \"method\": \"Live-cell imaging and surface antibody feeding assays in cultured rat neurons, microtubule co-sedimentation assay, patient allele mutagenesis, co-immunoprecipitation\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — multiple orthogonal methods (endocytosis assay, MT binding, patient allele functional test) in single study\",\n      \"pmids\": [\"22649224\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"DCX regulates filamentous actin (F-actin) structure in developing neurons. Loss of Dcx leads to increased F-actin around the cell body and decreased F-actin in neurites and growth cones. The C-terminal S/P-rich domain of DCX is required for this actin regulatory function, likely through interaction with spinophilin but not through α-actinin-4 or Arp3.\",\n      \"method\": \"Quantitative proteomics of corpus callosum from Dcx mutant mice, rescue experiments with full-length DCX and truncation/phospho-mutants, F-actin staining\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic analysis plus domain-mapping rescue experiments with specific mutants in neuronal cells\",\n      \"pmids\": [\"23303949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Cdk5 phosphorylates DCX to regulate cytoplasmic dilation formation and nuclear elongation in migrating cortical neurons. Pharmacological or RNAi-mediated inhibition of Cdk5 suppresses both dilation formation and nuclear elongation; knockdown of Dcx (a Cdk5 substrate involved in microtubule organization and membrane/endocytic trafficking) similarly disrupts these migrating-neuron-specific features.\",\n      \"method\": \"Chemical inhibitor experiments ex vivo, RNAi knockdown of Cdk5 and Dcx in migrating neurons, live imaging of neuronal migration\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi knockdown with specific phenotypic readout and epistasis; kinase-substrate relationship inferred from prior literature rather than demonstrated by in vitro assay in this paper\",\n      \"pmids\": [\"25183872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"RNAi knockdown of DCX or LIS1 in vivo disrupts neuronal migration along the lateral cortical stream (LCS) into the amygdala and piriform cortex. Combinatorial RNAi of both LIS1 and DCX further suggests a functional interaction between these proteins in migrating neurons in the LCS, affecting neuron morphology and migration.\",\n      \"method\": \"In utero electroporation with RNAi in mice, combinatorial knockdown epistasis analysis, histological readout of migration\",\n      \"journal\": \"Developmental neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo RNAi with epistasis analysis; no biochemical reconstitution of the interaction\",\n      \"pmids\": [\"18075262\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"DCX overexpression in PC12 cells stabilizes microtubules and inhibits neurite outgrowth under NGF-induced differentiation, but increases neurite length under EGF/forskolin or dibutyryl-cAMP treatment. DCX overexpression downregulates CREB-mediated transcription. A lissencephaly patient mutation (S47R) completely blocks neurite outgrowth. Microtubule stabilization is a key but not sole factor controlling neurite extension by DCX.\",\n      \"method\": \"Overexpression in PC12 cells, patient allele mutagenesis, microtubule stabilization assays, neurite outgrowth quantification, CREB reporter assays\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function plus patient allele mutagenesis with defined cellular readouts; single lab study\",\n      \"pmids\": [\"11331616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"DCX domain proteins as a superfamily share conserved roles in microtubule regulation: all tested DCX-domain proteins stimulate microtubule assembly in vitro. Proteins with tandem DCX repeats stabilize the microtubule cytoskeleton in transfected cells, while those with single repeats localize to actin-rich structures or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subset interacted with Neurabin 2, and a non-overlapping group showed actin association.\",\n      \"method\": \"In vitro microtubule assembly assay, transfection with immunofluorescence, co-immunoprecipitation\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro assembly assay and Co-IP for multiple family members; findings specific to canonical DCX confirmed but embedded in superfamily analysis\",\n      \"pmids\": [\"16628014\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Using iPSC-derived neural stem cells from DCX-mutant lissencephaly patients, absent or reduced DCX protein expression causes impaired migration, delayed differentiation, and deficient neurite formation, expanding the role of DCX beyond microtubule stabilization to include neuronal differentiation and neurite outgrowth.\",\n      \"method\": \"iPSC disease modeling, neural differentiation assays, expression profiling, migration assays in patient-derived cells\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient-derived iPSC model with defined phenotypic readouts; single lab, no biochemical reconstitution\",\n      \"pmids\": [\"28924182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Loss-of-function mutations in DCX (XLIS) cause X-linked lissencephaly in hemizygous males and subcortical band heterotopia in heterozygous carrier females, establishing DCX as required for normal neuronal migration. Point mutations in the C-terminal serine/proline-rich region identify this region as important for DCX function.\",\n      \"method\": \"Direct DNA sequencing of patients, genotype-phenotype correlation in LIS/SBH pedigrees\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Strong — genetic loss-of-function with defined brain malformation phenotype replicated across multiple studies; no biochemical mechanism established in this paper\",\n      \"pmids\": [\"9817918\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Doublecortin (DCX) is exclusively expressed in fetal brain and adult frontal lobe, encodes isoforms of a highly hydrophilic ~40 kDa protein with several potential phosphorylation sites, and is homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting DCX may function through Ca2+-dependent signaling. Mutations cause LIS/SBH.\",\n      \"method\": \"Gene cloning, Northern blot, protein sequence analysis, patient mutation identification\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence-based prediction of Ca2+-dependent signaling; no direct biochemical demonstration\",\n      \"pmids\": [\"9668176\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DCX (doublecortin) is a microtubule-associated protein expressed in migrating neurons that stabilizes microtubules via tandem DCX domains (N-terminal domain binds assembled microtubules; C-terminal domain binds both tubulin and microtubules), acts as an endocytic adaptor for neurofascin independently of microtubule binding, and functions as a signaling hub phosphorylated by JNK (at growth cones, scaffolded by JIP/kinesin), GSK3β (Ser327, restricting axon branching downstream of JIP3), and Cdk5, with site-specific dephosphorylation mediated by PP1 recruited via Neurabin II; its C-terminal S/P-rich domain additionally regulates F-actin distribution in neurites, and loss-of-function mutations cause lissencephaly and subcortical band heterotopia due to impaired neuronal migration, differentiation, and neurite formation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DCX (doublecortin) is a neuronal microtubule-associated protein required for cortical neuronal migration, whose loss-of-function mutations cause X-linked lissencephaly in males and subcortical band heterotopia in carrier females [#11]. Its structural basis lies in tandem DCX domains: the N-terminal domain adopts a ubiquitin-like fold and binds only assembled microtubules, while the partially folded C-terminal domain binds both microtubules and unpolymerized tubulin, enabling DCX to stimulate microtubule assembly and stabilize the cytoskeleton [#1, #9]. Beyond microtubule stabilization, DCX serves as an endocytic adaptor that promotes internalization of the cell adhesion molecule neurofascin independently of microtubule binding, and it shapes F-actin distribution in neurites through its C-terminal serine/proline-rich domain via spinophilin [#4, #5]. DCX integrates multiple signaling inputs as a phosphorylation hub: JNK phosphorylates DCX at growth cones with its localization set by JIP/kinesin, GSK3β phosphorylates Ser327 downstream of JIP3 to restrict axon branching, and Cdk5 regulates dilation formation and nuclear elongation in migrating neurons, with PP1 reversing JNK-site phosphorylation through Neurabin II recruitment [#0, #2, #3, #6]. Functionally, DCX cooperates with LIS1 in migrating neurons and is required not only for migration but also for neuronal differentiation and neurite formation [#7, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing that DCX is genetically required for neuronal migration defined the disease relevance and the core biological process the protein serves.\",\n      \"evidence\": \"DNA sequencing and genotype-phenotype correlation in lissencephaly/SBH pedigrees, plus gene cloning and expression profiling\",\n      \"pmids\": [\"9817918\", \"9668176\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical mechanism established\", \"C-terminal S/P-rich region implicated by mutation but its molecular role undefined\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Linking DCX overexpression to microtubule stabilization and altered neurite outgrowth began to connect its molecular activity to a cellular phenotype, while a patient allele showed migration biology is not purely microtubule-based.\",\n      \"evidence\": \"Overexpression and patient-allele mutagenesis in PC12 cells with microtubule and neurite-outgrowth readouts and CREB reporter assays\",\n      \"pmids\": [\"11331616\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell-line gain-of-function system\", \"Microtubule stabilization stated to be 'not sole factor' without identifying the others\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Solving the tandem DCX domain structures revealed the molecular basis for differential tubulin and microtubule binding, explaining how DCX engages the cytoskeleton.\",\n      \"evidence\": \"NMR and crystal structures of N-terminal domains plus in vitro microtubule/tubulin binding assays\",\n      \"pmids\": [\"12692530\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"C-terminal domain only partially folded and structurally unresolved\", \"Does not show how binding is regulated in cells\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Identifying DCX as a JNK substrate scaffolded by JIP/kinesin placed it within a signaling and transport framework controlling its localization and migration function.\",\n      \"evidence\": \"In vitro kinase assay, co-IP, phospho-site mutagenesis, and live imaging of migrating neurons\",\n      \"pmids\": [\"14765123\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of individual phospho-sites on microtubule binding not resolved\", \"How JNK signaling is spatially triggered at growth cones unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrating PP1/Neurabin II-mediated dephosphorylation and superfamily-wide microtubule activity established that DCX phosphorylation is dynamically reversible and that its cytoskeletal role is shared across DCX-domain proteins.\",\n      \"evidence\": \"In vitro phosphatase assay with RVXF-motif mutagenesis, co-IP, and in vitro microtubule assembly assays across family members\",\n      \"pmids\": [\"16530423\", \"16628014\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional impact of the PP1/JNK phospho-cycle on migration not directly tested\", \"Which kinase-phosphatase pairs operate at which subcellular sites unknown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showing a functional interaction between DCX and LIS1 in vivo connected DCX to a broader migration machinery.\",\n      \"evidence\": \"In utero electroporation RNAi with combinatorial knockdown epistasis and histological migration readout\",\n      \"pmids\": [\"18075262\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical reconstitution of the DCX-LIS1 interaction\", \"Mechanism of cooperativity unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Placing DCX in a JIP3-GSK3β pathway that phosphorylates Ser327 defined a discrete signaling axis restricting axon branching, distinct from JNK and Cdk5 inputs.\",\n      \"evidence\": \"In vitro kinase assay mapping Ser327 plus RNAi knockdown and epistasis in primary neurons, slices, and in vivo\",\n      \"pmids\": [\"21159948\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream effector of Ser327 phosphorylation not identified\", \"Whether Ser327 alters microtubule or actin binding unknown\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Discovering a microtubule-independent endocytic adaptor function for neurofascin expanded DCX beyond a cytoskeletal protein and explained a patient allele that retains microtubule binding yet causes disease.\",\n      \"evidence\": \"Live-cell surface-feeding endocytosis assays, microtubule co-sedimentation, patient-allele (G253D) mutagenesis, and co-IP in cultured neurons\",\n      \"pmids\": [\"22649224\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endocytic machinery partners DCX recruits are unidentified\", \"Relative contribution of endocytic vs microtubule function to migration not quantified\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mapping F-actin regulation to the C-terminal S/P-rich domain via spinophilin identified a second cytoskeletal axis controlled by DCX.\",\n      \"evidence\": \"Quantitative proteomics of Dcx-mutant corpus callosum with domain/phospho-mutant rescue and F-actin staining\",\n      \"pmids\": [\"23303949\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct DCX-spinophilin interaction mechanism not fully resolved\", \"α-actinin-4 and Arp3 excluded but the actin effector chain incomplete\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linking Cdk5-dependent DCX phosphorylation to cytoplasmic dilation and nuclear elongation tied DCX phospho-regulation to migration-specific cell-shape changes.\",\n      \"evidence\": \"Chemical inhibition and RNAi of Cdk5 and Dcx with live imaging of migrating neurons\",\n      \"pmids\": [\"25183872\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cdk5-DCX kinase-substrate relationship inferred rather than shown by in vitro assay in this study\", \"Specific Cdk5 phospho-sites driving the phenotype not mapped\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Patient iPSC-derived neural stem cell modeling demonstrated DCX is required for neuronal differentiation and neurite formation, broadening its role beyond migration.\",\n      \"evidence\": \"iPSC disease modeling with neural differentiation, expression profiling, and migration assays in patient-derived cells\",\n      \"pmids\": [\"28924182\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway linking DCX loss to differentiation delay not defined\", \"Single-lab model without biochemical reconstitution\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DCX's distinct activities — microtubule stabilization, actin regulation, and neurofascin endocytosis — are coordinated by its phosphorylation state at a given subcellular site to drive migration remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No integrated model connecting specific phospho-sites to each functional output\", \"Spatial-temporal switching between cytoskeletal and adaptor roles uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 8, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [7, 10, 11]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"JNK\", \"JIP\", \"JIP3\", \"GSK3B\", \"PPP1CA\", \"PPP1R9B\", \"NFASC\", \"LIS1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}