Calcium-binding protein (CaBP) (CaBP)

Calcium-binding proteins (CaBPs) are a large and diverse family of proteins that serve as essential mediators of calcium signaling by binding Ca2+ ions through specialized structural motifs like the EF-hand, C2 domain, or annexin fold (UniProt: P62158). These proteins function either as calcium sensors, which undergo conformational changes to regulate downstream effectors, or as calcium buffers, which regulate the spatial and temporal dynamics of intracellular calcium concentrations (PubMed: 24012071). Prominent members include calmodulin, which regulates a vast array of enzymes and ion channels, and troponin C, which triggers muscle contraction in response to calcium influx (StatPearls: NBK544316). In various disease states, the expression or function of CaBPs is often altered; for instance, S100 proteins are frequently upregulated in inflammatory conditions and various cancers, contributing to tumor progression and metastasis (PubMed: 28233003). Therapeutic intervention targeting CaBPs includes the use of calcium sensitizers like levosimendan for heart failure, which increases the affinity of troponin C for calcium, and certain antipsychotics like trifluoperazine that inhibit calmodulin (PubChem: CID 5510). Additionally, CaBPs such as troponin and calprotectin serve as critical clinical biomarkers for myocardial infarction and inflammatory bowel disease, respectively (PubMed: 30003017). Developing drugs for this class is challenging due to the high structural conservation of calcium-binding sites, which can lead to significant off-target effects and systemic toxicity (PubMed: 2535556).

Other names

Calcium-modulated proteinEF-hand proteinCalcium sensorCalcium bufferPhysiological calcium-binding proteins and sites

Modulation of calcium-dependent conformational changes to either enhance (sensitize) or inhibit (antagonize) interactions with downstream effector proteins (StatPearls: NBK544316).