Recombinant Human Cysteine and glycine-rich protein 3 (CSRP3)

Function

May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization

Subcellular Location

Cytoplasm, myofibril, sarcomere, Z line

Disease Association

Cardiomyopathy, dilated, 1M (CMD1M) : A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. [The disease is caused by variants affecting the gene represented in this entry] | Cardiomyopathy, familial hypertrophic, 12 (CMH12) : A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Cardiac and slow-twitch skeletal muscles. Isoform 2 is expressed in striated muscle. Isoform 2 is specifically expressed at higher levels in patients with neuromuscular diseases, such as limb-girdle muscular dystrophy 2A (LGMD2A), Duchenne muscular dystrophy (DMD) and dermatomyositis (PubMed:24860983)

Subunit

Self-associates. Oligomeric in the cytoplasm and monomeric in the nucleus (By similarity). Homooligomers preferentially form along the actin cytoskeleton. Isoform 2 interacts with isoform 1 (PubMed:24860983, PubMed:24934443). Isoform 1 but not isoform 2 interacts with MYOD1 and MYOG. Isoform 1 interacts with TCAP, ACTN2 and NRAP. Isoform 2 interacts with TCAP and alpha-actinin (PubMed:12507422, PubMed:15205937, PubMed:15582318, PubMed:24860983). Interacts with LDHD. Interacts (via N-terminus)with GLRX3 (via C-terminus) and PPP3CA; GLRX3 and calcineurin compete for interaction with CSRP3. Interacts with MYF6 (By similarity). Interacts with CFL2; the stoichiometry influences F-actin depolymerization and possibly two molecules of CFL2 can interact with one molecule of CSRP3 resulting in the highest functional impact; the interaction is stronger with phosphorylated CFL2 (PubMed:19752190)

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• Yasunaga S. et al. Cloning and characterization of the human muscle LIM protein gene. (OCT-)
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• Vafiadaki E. et al. Muscle lim protein isoform negatively regulates striated muscle actin dynamics and differentiation. — FEBS J. (2014)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hayashi T. et al. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. — J. Am. Coll. Cardiol. (2004)
• Gehmlich K. et al. Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy. — Cell Tissue Res. (2004)