Calcium and integrin-binding protein 1 (CIB1)

Calcium and integrin-binding protein 1 (CIB1) is a small (~22 kDa) calcium-binding protein characterized by EF-hand domains, and functions as an adapter and regulatory molecule interacting with integrins (especially αIIbβ3 on platelets), various kinases (such as DNA-PKcs and ASK1), and other proteins involved in calcium signaling, apoptosis, cell adhesion, migration, and proliferation[1][2][3][4][5]. CIB1’s EF-hand domains bind calcium, inducing conformational changes that regulate its interactions, primarily with the cytoplasmic tail of integrins and proteins involved in stress response pathways such as MAPK[1][2][3][5]. CIB1 is widely expressed and plays pivotal roles in platelet aggregation, cardiac hypertrophy, atrial fibrillation, and cancer cell biology; dysregulation or upregulation is associated with several diseases, particularly cancer and cardiovascular disorders[2][3][5]. Despite structural similarities with calmodulin and calcineurin B, CIB1 is monomeric under physiological conditions and possesses distinct adaptor functions in signal transduction[2]. While there are currently no approved drugs directly targeting CIB1, its roles in critical signaling axes have made it of considerable therapeutic interest, but its ubiquitous physiological roles pose safety challenges for direct modulation[3][4].

Other names

Calcium- and integrin-binding protein 1CIB1CIBKIPPRKDCIPCIBPSIP2-28CalmyrinDNA-PKcs-interacting proteinKinase-interacting proteinSNK-interacting protein 2-28DNA-PK interaction proteinDNA-dependent protein kinase interacting proteinTesticular secretory protein Li 9EV3KIP1

Potential drugs would be expected to act by modulating CIB1’s protein-protein interactions (e.g., with integrins or kinase targets such as ASK1); Inhibition or modulation of calcium-binding to block conformational activation; Disruption of CIB1-mediated scaffolding in signaling cascades.