FunctionMicrotubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.
Sequence similaritiesBelongs to the CLASP family. Contains 8 HEAT repeats.
DomainThe two SXIP sequence motifs mediate interaction with MAPRE1; this is necessary for targeting to growing microtubule plus ends. Two TOG regions display structural characteristics similar to HEAT repeat domains and mediate interaction with microtubules.
Post-translational modificationsPhosphorylated by GSK3B. Phosphorylation reduces MAPRE1 binding (PubMed:26003921). Phosphorylation by GSK3B may negatively regulate binding to microtubule lattices in lamella.
Cellular localizationCytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, spindle. Golgi apparatus. Golgi apparatus, trans-Golgi network. Cell membrane. Cell projection, ruffle membrane. Localizes to microtubule plus ends (PubMed:15631994). Localizes to centrosomes, kinetochores and the mitotic spindle from prometaphase. Subsequently localizes to the spindle midzone from anaphase and to the midbody from telophase (PubMed:16866869, PubMed:16914514). In migrating cells localizes to the plus ends of microtubules within the cell body and to the entire microtubule lattice within the lamella. Localizes to the cell cortex and this requires ERC1 and PHLDB2 (PubMed:16824950). The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane.