DCX (doublecortin) is a neuronal microtubule-associated protein built from two tandem doublecortin (DC) domains followed by a serine/proline-rich C-terminal region. It is expressed in migrating and differentiating neurons of the developing central and peripheral nervous system and in adult neurogenic niches. DCX binds the microtubule lattice in the groove between protofilaments, selectively and cooperatively recognizing 13-protofilament microtubules; it promotes tubulin polymerization and nucleation of 13-protofilament microtubules in vitro and stabilizes microtubules against depolymerization. In cells it decorates the GDP lattice rather than growing plus ends, and is enriched in leading processes, growth cones and neurite tips. Phosphorylation by PKA, MARK/PAR-1 and other kinases lowers its microtubule affinity at the leading edge. In migrating neurons DCX outlines the perinuclear microtubule cage that converges on the centrosome and associates with LIS1 and dynein, supporting nucleus-centrosome coupling during nucleokinesis. DCX is required for radial migration of cortical neurons; loss-of-function variants cause X-linked lissencephaly in males and subcortical band heterotopia (double cortex) in females, many of which weaken microtubule binding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001764 neuron migration | IDA PMID:14741102 Doublecortin microtubule affinity is regulated by a balance ... | ACCEPT | Summary: DCX is required for neuronal migration; its leading-process localization and phospho-regulation are linked to migration. Reason: Neuron migration is the defining biological role of DCX: human mutations cause X-linked lissencephaly and subcortical band heterotopia, in utero RNAi in rat blocks radial migration, and DCX is enriched in leading processes of migrating neurons. Supporting Evidence: PMID:14625554 we show that DCX is required for radial migration in developing rat neocortex PMID:14741102 Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons file:human/DCX/DCX-uniprot.txt Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. |
| GO:0001764 neuron migration | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (DCX chordate family IPR017302) mapping to neuron migration. Reason: Neuron migration is the defining biological role of DCX: human mutations cause X-linked lissencephaly and subcortical band heterotopia, in utero RNAi in rat blocks radial migration, and DCX is enriched in leading processes of migrating neurons. Supporting Evidence: PMID:14625554 we show that DCX is required for radial migration in developing rat neocortex PMID:14741102 Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons file:human/DCX/DCX-uniprot.txt Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | UNDECIDED | Summary: The DCX–TINF2 screen annotation remains unresolved because the individual positive hit could not be re-inspected. Reason: The cached PMID:21044950 body contains the Abstract and Discussion, not the hit-level evidence or complete Methods/Results. Full-original recovery attempts did not yield readable article text, and current target- and TINF2-scoped IntAct/MINT searches did not recover this pair. These are access and source-recovery limits, not evidence against the original curator. TINF2 is a shelterin component, but neither a telomere role nor a narrower binding activity for DCX can be assigned from that identity alone. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Refine the DCX–GOLGA2 Y2H interaction to cytoskeletal regulatory protein binding. Reason: The positive PMID:21516116 Y2H record identifies O43602/Q08379. Original PMID:26165940 Figures 4–6 show that GM130 relieves TPX2 inhibition and promotes microtubule nucleation and capture/bundling, establishing the partner class in GO:0005519; PMID:19242490 provides complementary abstract-level evidence. GM130 is accessible on the cytoplasmic face of Golgi membranes. This qualitative binding capacity does not establish a native neuronal DCX–GM130 complex or assign Golgi or spindle activity to DCX. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-8646741|imex:IM-15361-514|mint:MINT-8168879 |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Refine the DCX–IKZF1 yeast two-hybrid interaction to DNA-binding transcription factor binding. Reason: The positive PMID:21516116 Y2H record identifies O43602/Q13422, matching the displayed human IKZF1 product. IKZF1 is a sequence-specific DNA-binding transcription factor, supporting GO:0140297 for the observed qualitative binding capacity. Canonical IKZF1 is predominantly nuclear and prominent in lymphoid tissues; a native neuronal DCX complex is unestablished. Its retinal-progenitor role by similarity does not demonstrate this pair, and the cytoplasmic Ik6 isoform is not substituted for the screened product. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-8646828|imex:IM-15361-515|mint:MINT-8168888 |
| GO:0005515 protein binding | IPI PMID:24607389 Mutations in USP9X are associated with X-linked intellectual... | MODIFY | Summary: Co-immunoprecipitation of DCX with the deubiquitinase USP9X; the paper states DCX is an interacting protein of USP9X, not its substrate. Reason: The cited full-text study supports a more informative MF: binding to the ubiquitin-specific protease USP9X, which colocalizes with DCX in axonal growth cones. Generic protein binding should be replaced by ubiquitin-specific protease binding. This is a peripheral function of DCX. Proposed replacements: ubiquitin-specific protease binding Supporting Evidence: PMID:24607389 DCX coimmunoprecipitated with USP9X and all three variant forms in this assay PMID:24607389 Given the fact that DCX is not a USP9X substrate (rather, it is an interacting protein) |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the positive DCX–ZBTB5 Y2H screen interaction as non-core. Reason: The exact O43602/O15062 pair has positive PMID:25416956 records for the screen, array and validated-Y2H phases. The official ZBTB5 record says that it may participate in transcriptional regulation; its zinc-finger/BTB architecture alone does not establish the sequence-specific DNA-binding transcription-factor class required by GO:0140297. Keep the supported interaction without inventing a transcriptional or adaptor activity for DCX. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503548|imex:IM-23318-30709 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–TRIM27 Y2H interaction to ubiquitin protein ligase binding. Reason: Positive PMID:25416956 records identify O43602/P14373 in pooled-screen, array and validated-Y2H stages of one study. TRIM27 is a verified E3 ligase with cytoplasmic, nuclear and endosomal locations, supporting GO:0031625 for the observed qualitative binding capacity. Native neuronal interaction and DCX substrate status are unestablished; the pair does not assign ubiquitination or the partner’s immune and autophagy functions to DCX. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503558|imex:IM-23318-30710 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–TRIM23 Y2H interaction to ubiquitin protein ligase binding. Reason: Positive PMID:25416956 records identify O43602/P36406 across three Y2H stages of one study. TRIM23 is an E3 ligase with an additional ARF GTPase region and cytoplasmic/Golgi localization, supporting GO:0031625 for the qualitative binding capacity. The assay does not identify the contacted domain or establish a native neuronal complex, DCX substrate status or GTPase regulation. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503568|imex:IM-23318-30711 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–MEOX1 Y2H interaction to DNA-binding transcription factor binding. Reason: Positive PMID:25416956 records identify O43602/P50221 across three Y2H stages of one study. MEOX1 binds target promoters and modulates transcription, satisfying the partner class in GO:0140297. Its mesodermal functions and predominantly nuclear localization leave the native neuronal relevance uncertain; cytoplasmic localization by similarity is not evidence for this pair. Retain the observed qualitative binding capacity without inferring coexpression, a native complex or transcriptional activity of DCX. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10525128|imex:IM-23318-32808 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the positive DCX–KRTAP10-8 Y2H interaction as non-core. Reason: The exact O43602/P60410 pair has positive PMID:25416956 screen, array and validated-Y2H records. KRTAP10-8 is a keratin-associated interfilamentous matrix protein, not an individual keratin or an assembled keratin filament. The interaction therefore does not justify keratin filament binding or a hair-shaft structural activity for DCX. Retain the experimental association without a speculative class or pathway transfer. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10531518|imex:IM-23318-33438 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–GOLGA2 Y2H interaction to cytoskeletal regulatory protein binding. Reason: Positive PMID:25416956 records identify O43602/Q08379 across three Y2H stages of one study. Original PMID:26165940 Figures 4–6 establish GM130-dependent TPX2 activation, microtubule nucleation and capture/bundling, supporting the cytoskeletal-regulator class in GO:0005519. Cytoplasmic Golgi-surface localization permits physical access but does not demonstrate a native neuronal DCX complex. The qualitative pair result assigns no GM130 mechanism or spindle activity to DCX. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503578|imex:IM-23318-30712 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the positive DCX–CALCOCO2 Y2H interaction as non-core. Reason: The exact O43602/Q13137 pair is positive in the PMID:25416956 screen, array and validated-Y2H records. CALCOCO2 is a selective-autophagy cargo receptor, but this association does not demonstrate DCX cargo-receptor activity, autophagic recruitment or simultaneous adaptor contacts. No inspected narrower binding term is justified merely from the partner’s pathway membership. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503588|imex:IM-23318-30713 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the PMID:25416956 DCX–IKZF1 Y2H interaction to DNA-binding transcription factor binding. Reason: Positive PMID:25416956 records identify O43602/Q13422 across three Y2H stages of one study, with sequences matching the displayed human products. IKZF1’s DNA-binding transcription-factor role supports GO:0140297 for the qualitative binding capacity. Its predominantly nuclear and lymphoid context leaves native neuronal relevance unestablished. The separate PMID:21516116 pair is additional screen evidence, not proof of endogenous colocalization; neither Ik6 localization nor the unrelated DDB1–CUL4–X-box “DCX” acronym is used as support. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503598|imex:IM-23318-30714 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–KRT40 Y2H interaction to cytoskeletal protein binding. Reason: Positive PMID:25416956 records identify O43602/Q6A162 across three Y2H stages of one study. KRT40 is an intermediate-filament keratin, supporting GO:0008092 for binding to the individual cytoskeletal protein. Its hair-cuticle-enriched expression makes a native neuronal complex particularly uncertain; no coexpression is demonstrated. The qualitative pair assay does not establish polymerized-filament binding or a core keratin function. Existing microtubule-binding evidence does not itself document this distinct KRT40 interaction. Proposed replacements: cytoskeletal protein binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10566022|imex:IM-23318-36816 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Retain the positive PMID:25416956 DCX–RINT1 Y2H interaction as non-core. Reason: Positive screen, array and validated-Y2H records identify the exact O43602/Q6NUQ1 pair under PMID:25416956. RINT1’s roles in membrane-traffic tethering complexes do not by themselves establish a DCX tethering, signaling-adaptor or signaling-scaffold-binding activity. This source row reports a supported interaction without the separate position-660 variant feature of the PMID:31515488 record; retain its own evidence scope. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10570260|imex:IM-23318-37234 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–SPAG5 Y2H interaction to cytoskeletal protein binding. Reason: Positive PMID:25416956 records identify O43602/Q96R06 across three Y2H stages of one study. SPAG5/astrin is a spindle-associated cytoskeletal protein, supporting GO:0008092. Its official record also reports a microtubule pattern in unstressed nonmitotic cells, so a mitosis-only compartment exclusion is unsupported. The qualitative binding capacity establishes neither a native neuronal DCX complex nor binding to an assembled spindle, and assigns no mitotic or centrosomal activity to DCX. Proposed replacements: cytoskeletal protein binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503608|imex:IM-23318-30715 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the DCX–KIFC3 Y2H interaction to kinesin binding. Reason: Positive PMID:25416956 records identify O43602/Q9BVG8 across three Y2H stages of one study. KIFC3 is a verified kinesin-family motor, supporting GO:0019894 for the controlled binary binding capacity. The current definition includes selective, noncovalent and stoichiometric binding; these qualitative assays do not measure a binding constant or complex ratio. No contrary result rules out that binding class, but a quantitative stoichiometry, native neuronal complex, motor regulation or cargo-coupling mechanism is not established. Proposed replacements: kinesin binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10611926|imex:IM-23318-41323 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Refine the construct-scoped DCX–MID2 isoform-2 Y2H interaction to ubiquitin protein ligase binding. Reason: Positive PMID:25416956 records identify O43602 and Q9UJV3-2. The 705-residue MID2 isoform is reconstructed by deleting residues 450–479 from the displayed 735-residue sequence. Screen/array records specify a sufficient-binding region at residues 21–705; the validated-Y2H record has no feature annotation. The region retains the RING domain of the E3-class partner, supporting GO:0031625 for qualitative binding. Neither construct catalytic activity, a native neuronal complex, DCX substrate status nor full-length or isoform-exclusive binding is established. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-10503618|imex:IM-23318-30716 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Retain the DCX–RINT1 interaction tested with a RINT1 position-660 variant as non-core. Reason: The PMID:31515488 IntAct record identifies O43602/Q6NUQ1, is not negative, and marks the partner’s rs35531972 feature at residue 660 as “mutation with no effect”. The original Methods compare WT and mutant interactions and require reproducible growth reduction to call disruption; the paper title does not mean that this pair was disrupted. The feature belongs to RINT1, not DCX. Retain the positive variant-tested interaction without claiming the variant is generally benign, adding an isoform flag, or assigning DCX a membrane-tethering function. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-22126042|imex:IM-27438-2024 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the DCX–ZBTB5 BioPlex association in HCT116 cells as non-core. Reason: The PMID:33961781 record identifies C-terminally tandem-tagged DCX as bait and ZBTB5 as prey in HCT116 cells. BioPlex anti-tag affinity purification/MS supports association and can recover indirect co-complex edges; it does not establish direct binding for this pair. Moreover, ZBTB5’s incompletely characterized transcriptional role does not justify a DNA-binding transcription-factor class refinement. Keep the positive association without a transcriptional or neuronal mechanism. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-54909443|imex:IM-29278-20735 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the DCX–AGMAT BioPlex association in HEK293T and HCT116 cells as non-core. Reason: Two PMID:33961781 records identify C-terminally tandem-tagged AGMAT bait with DCX prey, one in HEK293T and one in HCT116 cells. These are supported AP-MS associations, not proof of direct enzyme binding. The current official partner record identifies AGMAT as a guanidino acid hydrolase and cautions that the historical agmatinase assignment was not demonstrated with purified enzyme. No specific enzyme-binding refinement, catalytic function, substrate relation or metabolic pathway role is assigned to DCX from these co-complex edges. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml intact:EBI-54681992|imex:IM-29278-6161 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (UniProt subcellular location mapping). Reason: DCX is a cytoplasmic microtubule-associated protein; correct general location. Supporting Evidence: PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol localization (HPA immunofluorescence IDA; Reactome TAS from the neurofascin-binding event). Reason: DCX is a soluble cytoplasmic MAP distributed along microtubules; cytosol is a correct if broad location. Supporting Evidence: PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-443772 | ACCEPT | Summary: Cytosol localization (HPA immunofluorescence IDA; Reactome TAS from the neurofascin-binding event). Reason: DCX is a soluble cytoplasmic MAP distributed along microtubules; cytosol is a correct if broad location. Supporting Evidence: PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. |
| GO:0005856 cytoskeleton | TAS PMID:11001923 Interaction between LIS1 and doublecortin, two lissencephaly... | ACCEPT | Summary: Cytoskeleton (TAS, LIS1-DCX interaction study). Reason: DCX associates with tubulin and microtubules; cytoskeleton is a correct general location. Supporting Evidence: PMID:11001923 LIS1 and DCX interact with tubulin and microtubules. PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. |
| GO:0005875 microtubule associated complex | TAS PMID:11001923 Interaction between LIS1 and doublecortin, two lissencephaly... | MODIFY | Summary: TAS: part of microtubule associated complex, from the LIS1-DCX interaction study. Reason: DCX is a microtubule lattice-binding MAP rather than a stable subunit of a defined multimeric complex. Its location is better stated as microtubule (located_in), which is directly supported by colocalization and co-sedimentation with microtubules. Proposed replacements: microtubule Supporting Evidence: PMID:11001923 LIS1 and DCX interact with tubulin and microtubules. PMID:15173193 Cotransduction with Dcx-RFP and GFP-tubulin shows Dcx localizes on the MTs. PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. |
| GO:0007399 nervous system development | TAS PMID:9489699 A novel CNS gene required for neuronal migration and involve... | KEEP AS NON CORE | Summary: TAS: nervous system development, from the gene discovery paper. Reason: Correct but very broad; DCX's contribution to nervous system development is through neuronal migration, which is annotated directly. Supporting Evidence: PMID:9489699 This novel gene is highly expressed during brain development, mainly in fetal neurons including precursors. PMID:9489699 The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion. |
| GO:0007417 central nervous system development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Central nervous system development (ARBA IEA; TAS from gene discovery paper). Reason: Correct but broad; DCX's CNS developmental role is cortical neuron migration and lamination, captured by neuron migration. Supporting Evidence: PMID:9489699 The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion. file:human/DCX/DCX-uniprot.txt Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. |
| GO:0007417 central nervous system development | TAS PMID:9489699 A novel CNS gene required for neuronal migration and involve... | KEEP AS NON CORE | Summary: Central nervous system development (ARBA IEA; TAS from gene discovery paper). Reason: Correct but broad; DCX's CNS developmental role is cortical neuron migration and lamination, captured by neuron migration. Supporting Evidence: PMID:9489699 The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion. file:human/DCX/DCX-uniprot.txt Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. |
| GO:0008017 microtubule binding | IDA PMID:14741102 Doublecortin microtubule affinity is regulated by a balance ... | ACCEPT | Summary: DCX binds microtubules; binding is regulated by PKA and MARK phosphorylation. Reason: Microtubule binding is the core molecular function of DCX: it co-assembles with microtubules, binds between protofilaments selectively on 13-protofilament lattices, and patient mutations weaken binding. Supporting Evidence: PMID:14741102 We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases. PMID:27292316 Functional study showed that the mutant doublecortin protein had a significant reduction of its ability to bind microtubules. PMID:15200960 doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping of microtubule binding for the DCX family. Reason: Microtubule binding is the core molecular function of DCX: it co-assembles with microtubules, binds between protofilaments selectively on 13-protofilament lattices, and patient mutations weaken binding. Supporting Evidence: PMID:10399932 We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. PMID:15200960 doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization |
| GO:0008017 microtubule binding | IMP PMID:27292316 A novel DCX missense mutation in a family with X-linked liss... | ACCEPT | Summary: A patient DCX missense variant (D262G) reduces microtubule binding. Reason: Microtubule binding is the core molecular function of DCX: it co-assembles with microtubules, binds between protofilaments selectively on 13-protofilament lattices, and patient mutations weaken binding. Supporting Evidence: PMID:14741102 We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases. PMID:27292316 Functional study showed that the mutant doublecortin protein had a significant reduction of its ability to bind microtubules. PMID:15200960 doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization |
| GO:0019901 protein kinase binding | IPI PMID:14741102 Doublecortin microtubule affinity is regulated by a balance ... | KEEP AS NON CORE | Summary: IPI with rat MARK2 (O08679): DCX interacts with and is phosphorylated by MARK/PAR-1 kinases. Reason: DCX is a substrate of PKA and MARK kinases that control its microtubule affinity; the curator recorded the interaction with MARK2 from the full text (abstract only available here). The binding reflects substrate recognition rather than a DCX function, so it is kept as non-core. Supporting Evidence: PMID:14741102 We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases. |
| GO:0035082 axoneme assembly | IEA GO_REF:0000002 | UNDECIDED | Summary: The axoneme-assembly mapping is present and targets DCX, but its biological applicability remains unresolved. Reason: IPR017302 is the chordate neuronal-migration doublecortin family, integrated from PIRSF037870, and matches the full 365-residue human DCX product. Its current mapping includes GO:0035082, whose definition concerns ciliary or flagellar axoneme assembly. The inspected source narrative does not identify the experiment or curator rationale for this particular mapping. General microtubule binding and neuronal localization neither establish nor contradict the process, and no target-specific negative result or wrong-paralog transfer was demonstrated. Biological applicability therefore remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR017302 · Neuronal migration protein doublecortin, chordates UNRESOLVED Verified DCX-family entry, PIRSF037870 target match 1–365 and current term mapping. Entry narrative does not establish this target process; no wrong-paralog source was demonstrated. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml InterPro:IPR017302 Neuronal migration protein doublecortin, chordates > GO:axoneme assembly ; GO:0035082 |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain intracellular signal transduction as a contextual process supported by DCX-dependent signaling experiments. Reason: The two domain mappings and target matches are real. In the separately recovered original PMID:22367209 Results and Figure 6B, DCX knockdown in mouse neuronal progenitors reduced PACAP-induced active Rac1 measured by GST-PAK-CRIB pulldown. Figure 6C–E separately shows phosphomutant/Asef2 effects in heterologous cells. These data support contextual signaling participation beyond phosphorylation alone. The normal publication cache remains abstract-only; the original supports this scoped claim. Native human mechanism, direct GEF activity and an exact adaptor mechanism are unestablished, so retain the existing broad IEA as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR003533 · Doublecortin domain SOURCE WEAK OR INFERRED Verified domain/superfamily target matches and current signal-transduction mapping. Domain presence alone is insufficient; separate mouse DCX signaling experiments support contextual retention. InterPro:IPR036572 · Doublecortin domain superfamily SOURCE WEAK OR INFERRED Verified domain/superfamily target matches and current signal-transduction mapping. Domain presence alone is insufficient; separate mouse DCX signaling experiments support contextual retention. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml InterPro:IPR003533 Doublecortin domain > GO:intracellular signal transduction ; GO:0035556 file:human/DCX/DCX-source-evidence.yaml InterPro:IPR036572 Doublecortin domain superfamily > GO:intracellular signal transduction ; GO:0035556 |
| GO:0043005 neuron projection | IDA PMID:14741102 Doublecortin microtubule affinity is regulated by a balance ... | ACCEPT | Summary: DCX localizes to neuron projections (leading processes, growth cones, neurite tips). Reason: DCX is enriched in leading processes of migrating neurons and in the distal parts of growing neurites and axons of differentiating neurons. Supporting Evidence: PMID:14741102 Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons PMID:10399932 Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neurons, and a strong axonal labeling is observed in differentiating neurons. |
| GO:0043005 neuron projection | IEA GO_REF:0000120 | ACCEPT | Summary: DCX localizes to neuron projections (leading processes, growth cones, neurite tips). Reason: DCX is enriched in leading processes of migrating neurons and in the distal parts of growing neurites and axons of differentiating neurons. Supporting Evidence: PMID:14741102 Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons PMID:10399932 Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neurons, and a strong axonal labeling is observed in differentiating neurons. |
| GO:0060041 retina development in camera-type eye | IEA GO_REF:0000002 | UNDECIDED | Summary: The retina-development mapping is present, but expression evidence does not settle a developmental function for human DCX. Reason: IPR017302 is a DCX-specific chordate family with a full-length target match, and its current GO mapping includes GO:0060041; a wrong-paralog propagation error has not been established. The inspected abstract of PMID:12752371 documents DCX expression/localization during rat retinal development and proposes a role; it does not establish a developmental step performed by DCX, and the complete original was not reviewed. Cortical disease phenotypes do not exclude retinal function. The mapping therefore remains unresolved rather than being categorically removed or accepted solely from expression. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR017302 · Neuronal migration protein doublecortin, chordates UNRESOLVED Verified DCX-family entry, PIRSF037870 target match 1–365 and current term mapping. Entry narrative does not establish this target process; no wrong-paralog source was demonstrated. Supporting Evidence: file:human/DCX/DCX-source-evidence.yaml InterPro:IPR017302 Neuronal migration protein doublecortin, chordates > GO:retina development in camera-type eye ; GO:0060041 |
| GO:0007026 negative regulation of microtubule depolymerization | IDA PMID:10399933 Doublecortin is a microtubule-associated protein and is expr... | NEW | Summary: DCX stabilizes microtubules against depolymerization by binding between protofilaments. Reason: DCX-decorated microtubules resist depolymerization, and structural work shows DCX binds the inter-protofilament groove, a site ideal for stabilization. DCX itself performs the stabilizing work (lattice binding), so it participates in the process. This is the process-level description of DCX's core activity and is how other stabilizing MAPs are annotated. Supporting Evidence: PMID:10399933 overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization PMID:15200960 doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization PMID:15200960 Doublecortin stabilizes microtubules and stimulates their polymerization but has no homology with other MAPs. file:human/DCX/DCX-deep-research-falcon.md Early biochemical work showed that DCX colocalizes and coassembles with microtubules, promotes polymerization and bundling, and renders a fraction of microtubules resistant to colchicine and cold-induced depolymerization. |
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Download this section (compressed HTML)Q: Is DCX's contribution to nucleokinesis purely as a stabilizer of the perinuclear microtubule track, or does its reported association with LIS1/dynein directly affect dynein force generation on the nucleus?
Q: To what extent does DCLK1 redundancy explain the mild cortical phenotype of Dcx-null mice versus the severe human and rat RNAi phenotypes, and does this bear on nucleokinesis specifically?
Q: Does CDK5 phosphorylation of DCX (Ser297), which reportedly controls DCX association with thin perinuclear microtubules, regulate the perinuclear cage during nucleokinesis, and are DCX effects on kinesin-3 cargo transport direct?
Experiment: Live imaging of nucleus-centrosome coupling in DCX-null human iPSC-derived cortical neurons, rescued with wild-type DCX or patient variants that selectively weaken microtubule binding versus LIS1 association, to separate track-stabilization from motor-associated roles.
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