| Structural highlights
Disease
CASQ2_HUMAN Defects in CASQ2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) [MIM:611938; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT2 is an autosomal recessive form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death.[1] [2] [3] [4] [5]
Function
CASQ2_HUMAN Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction. The skeletal muscle isoform (CASQ1) binds around 80 Ca(2+) ions, while the cardiac isoform (CASQ2) binds approximately 60 Ca(2+) ions.[6]
References
- ↑ Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C. Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003 doi:10.1016/j.jmb.2007.08.055
- ↑ Lahat H, Pras E, Olender T, Avidan N, Ben-Asher E, Man O, Levy-Nissenbaum E, Khoury A, Lorber A, Goldman B, Lancet D, Eldar M. A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Genet. 2001 Dec;69(6):1378-84. Epub 2001 Oct 25. PMID:11704930 doi:S0002-9297(07)61266-X
- ↑ Houle TD, Ram ML, Cala SE. Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium. Cardiovasc Res. 2004 Nov 1;64(2):227-33. PMID:15485681 doi:S0008-6363(04)00394-3
- ↑ di Barletta MR, Viatchenko-Karpinski S, Nori A, Memmi M, Terentyev D, Turcato F, Valle G, Rizzi N, Napolitano C, Gyorke S, Volpe P, Priori SG. Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2006 Sep 5;114(10):1012-9. Epub 2006 Aug 14. PMID:16908766 doi:CIRCULATIONAHA.106.623793
- ↑ Valle G, Galla D, Nori A, Priori SG, Gyorke S, de Filippis V, Volpe P. Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin. Biochem J. 2008 Jul 15;413(2):291-303. PMID:18399795 doi:BJ20080163
- ↑ Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C. Characterization of human cardiac calsequestrin and its deleterious mutants. J Mol Biol. 2007 Nov 2;373(4):1047-57. Epub 2007 Aug 29. PMID:17881003 doi:10.1016/j.jmb.2007.08.055
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