Spindle and kinetochore-associated complex subunit 2 (SKA2)

Spindle and kinetochore-associated complex subunit 2 (SKA2) is a small, highly conserved protein encoded by the SKA2 gene in humans, which forms part of the SKA complex (with SKA1 and SKA3). This complex is essential for proper chromosome segregation during mitosis, specifically facilitating the timely onset of anaphase by enabling the stable attachment of spindle microtubules to kinetochores. Beyond its core mitotic role, SKA2 interacts directly with the glucocorticoid receptor (GR), enhancing its nuclear translocation in neurons and peripheral tissues, which has implications for regulation of the hypothalamic–pituitary–adrenal (HPA) axis, stress response, and psychiatric disease mechanisms. SKA2 also modulates secretory autophagy in the brain, intersecting neuroinflammatory pathways linked to neurodegeneration. Clinically, altered SKA2 DNA methylation is studied as a potential biomarker for suicide risk and post-traumatic stress disorder, and its coordinated expression with PRR11 has a proposed role in lung cancer proliferation[1][2][4][7].

Other names

FAM33AProtein FAM33Aspindle and KT (kinetochore) associated 2spindle and kinetochore-associated protein 2family with sequence similarity 33, member AFLJ12758

Not drug-targeted; mechanistically, SKA2 enhances glucocorticoid receptor signaling through promoting FKBP4 interaction and modulates nuclear translocation of the glucocorticoid receptor[2].