SKA1
Function
Component of the SKA complex, a microtubule plus end-binding complex of the outer kinetochore that stabilizes spindle microtubule-kinetochore attachments, promotes alignment of chromosomes at the mitotic spindle equator (chromosome congression) and assists suppression of the spindle assembly checkpoint (PubMed:17093495, PubMed:19289083, PubMed:22371557, PubMed:22483620, PubMed:23085020, PubMed:26981768, PubMed:27697923, PubMed:29487209, PubMed:31804178). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:19289083, PubMed:22483620, PubMed:23085020, PubMed:28479321, PubMed:29487209). The outer kinetochore is made up of the ten-subunit KMN network complex, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components such as the SKA complex; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17093495, PubMed:19289083, PubMed:23085020, PubMed:28479321, PubMed:29487209). The SKA complex is loaded onto bioriented kinetochores and it facilitates chromosome congression by stabilizing microtubules together with MAPRE1, and end-on attachment of the NDC80 complex to depolymerizing spindle microtubules, thereby assisting the poleward-moving kinetochore in withstanding microtubule pulling forces (PubMed:19289083, PubMed:22371557, PubMed:22454517, PubMed:23085020, PubMed:24413531, PubMed:27697923, PubMed:28479321, PubMed:28495837, PubMed:29487209). The complex associates with dynamic microtubule plus-ends and can track both depolymerizing and elongating microtubules (PubMed:23085020, PubMed:29153323). The complex recruits protein phosphatase 1 (PP1) to the kinetochore in prometaphase and metaphase, to oppose spindle assembly checkpoint signaling and promote the onset of anaphase (PubMed:26981768). In the complex, it mediates interactions with microtubules (PubMed:19289083, PubMed:22483620, PubMed:23085020, PubMed:24413531, PubMed:27667719, PubMed:29153323, PubMed:36592928). It also stimulates AURKB/Aurora B catalytic activity (PubMed:27697923). During meiosis the SKA complex stabilizes the meiotic spindle and is required for its migration to the cortex (By similarity).
Post-translational modifications
Phosphorylated by AURKB at Thr-157 and Ser-242 which negatively regulates the association of the SKA complex with kinetochores to allow correction of aberrant kinetochore-microtubule interactions and promote mitotic sister chromatid biorientation.
Sequence Similarities
Belongs to the SKA1 family.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Spindle
- Chromosome
- Centromere
- Kinetochore
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Localizes to bioriented kinetochores and spindle microtubules during metaphase in a NDC80 complex-dependent manner (PubMed:17093495, PubMed:28479321, PubMed:29487209). The SKA complex begins to concentrate at kinetochores before microtubule attachment but reaches maximum levels on bioriented metaphase chromosomes (PubMed:17093495). Localizes both to microtubule plus-ends and along the length of microtubules (PubMed:27225956). The localization of the SKA complex to kinetochores is positively regulated by protein serine/threonine kinase CDK1 (PubMed:28479321). The localization of the SKA complex to kinetochores is negatively regulated by protein serine/threonine kinase AURKB, and this action is opposed directly or indirectly by the PP1 and PP2A protein phosphatase complexes (PubMed:22371557, PubMed:27697923). Localizes at the centrosome during interphase and prophase (PubMed:19646878). Localizes to the meiotic spindle, but not to kinetochores, from the stage of germinal vesicle breakdown (GVBD) to meiosis II (MII) (By similarity).
Alternative names
C18orf24, SKA1, SKA complex subunit 1, Spindle and kinetochore-associated protein 1