CKAP5

Domain

The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice.

Function

Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448).

Sequence Similarities

Belongs to the TOG/XMAP215 family.

Tissue Specificity

Overexpressed in hepatomas and colonic tumors. Also expressed in skeletal muscle, brain, heart, placenta, lung, liver, kidney and pancreas. Expression is elevated in the brain; highly expressed in the Purkinje cell bodies of the cerebellum.

Cellular localization

• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cytoskeleton
• Spindle pole
• Cytoplasm
• Cytoskeleton
• Spindle
• Chromosome
• Centromere
• Kinetochore
• Detected on centrosomes and kinetochores during interphase and mitosis independently from TACC3 and clathrin. Located to spindle poles and microtubules during mitosis. In complex with TACC3 localized to microtubule plus-ends in mitosis and interphase. In complex with TACC3 and clathrin localized to inter-microtubule bridges in mitotic spindles. Accumulation sites at microtubule plus ends protruded approximately 100 nm from MAPRE1/EB1 sites in interphase cells.

Alternative names

KIAA0097, CKAP5, Cytoskeleton-associated protein 5, Colonic and hepatic tumor overexpressed gene protein, Ch-TOG

Database links

swissprot:Q14008 omim:611142 entrezGene:9793 swissprot:Q0VAX7 swissprot:Q0VAX8 swissprot:Q8IYN5