DCX review notes

Journal for the DCX (O43602, doublecortin) GO annotation review.

Sources used

UniProt O43602 (DCX-uniprot.txt).
Cached GOA-cited publications, plus papers cached for this review after PubMed eutils verification:
PMID:10399933, PMID:10399932, PMID:15200960, PMID:22727374, PMID:14625554, PMID:27238282.
PMID:15173193 (Tanaka 2004) was already cached (module evidence).
Deep research (DCX-deep-research-falcon.md) was not present when the review was first drafted; see the end of
this file for the final check.

Neuronal microtubule-associated protein with two tandem doublecortin (DC) domains (UniProt DOMAIN 53..139,
180..263). Mutations cause X-linked lissencephaly (males) and subcortical band heterotopia (females)
PMID:9489699.
MAP that stabilizes microtubules and promotes polymerization
PMID:10399933,
PMID:10399933.
Binds between protofilaments, selective for 13-pf MTs PMID:15200960;
cooperative binding and 13-pf nucleation in vitro PMID:22727374; recognizes the compacted GDP lattice and is not a +TIP
in cells PMID:27238282.
Microtubule affinity is negatively regulated by PKA and MARK/PAR-1 phosphorylation PMID:14741102.
Required for radial migration in rat neocortex (in utero RNAi) PMID:14625554; mouse Dcx knockout has mild cortical
phenotype (redundancy with DCLK1) PMID:14625554.
Nucleokinesis: in mouse cerebellar granule neurons DCX outlines the perinuclear microtubule cage converging on the
centrosome, co-immunoprecipitates with dynein, and its overexpression rescues N-C coupling defects from Lis1 deficiency
and dynein inhibition PMID:15173193.
Interacts with LIS1 PMID:11001923 and USP9X (as interactor, not substrate) PMID:24607389.

Protein binding rows: REMOVE (uninformative; mostly proteome-scale screens), except USP9X row MODIFY to
GO:1990381 ubiquitin-specific protease binding (paper explicitly states DCX is an interacting protein, not a substrate).
InterPro2GO rows from IPR017302/IPR003533 for axoneme assembly, intracellular signal transduction and retina development:
REMOVE -- the DC domain is a microtubule-binding module; ciliary/retinal functions belong to RP1/RP1L1 family members,
and there is no evidence DCX acts in signal transduction.
microtubule associated complex (TAS): MODIFY to GO:0005874 microtubule (DCX is a lattice-binding MAP, not a subunit of a
defined complex).
NEW: GO:0007026 negative regulation of microtubule depolymerization (PMID:10399933, PMID:15200960).
Nucleokinesis module: supports DCX annoton function GO:0008017 microtubule binding. Did not add a NEW nuclear-migration
process annotation: evidence is mouse-only and DCX acts on the track (MT stabilization), which is captured by the
MT-stabilization process term; flagged as suggested question.

DCX-deep-research-falcon.md appeared after the first draft and was read. It agrees with the MT-nucleating,
lattice-stabilizing MAP model (Gleeson 1999, Moores 2004, Manka & Moores 2020), PKA/MARK/CDK5 regulation, and
X-linked lissencephaly/SBH genetics. Cited in support of NEW GO:0007026.
Not annotated (emerging/indirect): 2023 iPSC preprint on tubulin polyglutamylation and lysosome processivity;
kinesin-3 (KIF1A/KIF1C) cargo effects; PKA-Ser47 -> Asef2/Rac1 actin coupling. CDK5 Ser297 control of
perinuclear microtubule association raised as a suggested question (relevant to nucleokinesis).