CASQ2

Calsequestrin-2
Identifiers
Symbol	?
HGNC	1514
OMIM	114251
RefSeq	NM_001232
UniProt	P31230
Search for Structures Swiss-model Domains InterPro

Calsequestrin-2 (CASQ2) is a protein encoded by the CASQ2 gene in humans. It is a high-capacity, moderate-affinity calcium-binding protein that plays a crucial role in the regulation of calcium ion concentration within the sarcoplasmic reticulum of cardiac muscle cells.

Function

Calsequestrin-2 is primarily found in the sarcoplasmic reticulum of cardiac muscle cells, where it serves as a major calcium storage protein. It binds calcium ions with moderate affinity but high capacity, allowing the sarcoplasmic reticulum to sequester large amounts of calcium. This storage is essential for the proper functioning of cardiac muscle contraction and relaxation cycles.

During muscle contraction, calcium ions are released from the sarcoplasmic reticulum into the cytoplasm, triggering the interaction between actin and myosin filaments, which leads to muscle contraction. Calsequestrin-2 helps regulate this process by buffering calcium ions and ensuring their rapid release and uptake.

Clinical Significance

Mutations in the CASQ2 gene have been associated with Catecholaminergic polymorphic ventricular tachycardia (CPVT), a rare genetic disorder characterized by abnormal heart rhythms in response to physical activity or stress. CPVT can lead to syncope, seizures, or sudden cardiac death if not properly managed.

CASQ2 mutations disrupt the normal calcium buffering capacity of calsequestrin-2, leading to abnormal calcium handling in cardiac cells. This can result in arrhythmias due to inappropriate calcium release during the cardiac cycle.

Research

Research into CASQ2 and its role in cardiac physiology and pathology is ongoing. Studies focus on understanding the molecular mechanisms by which CASQ2 mutations lead to CPVT and exploring potential therapeutic interventions to correct or mitigate these effects.

Also see

• Sarcoplasmic reticulum
• Calcium signaling
• Cardiac muscle
• Catecholaminergic polymorphic ventricular tachycardia
• Calcium-binding proteins