CSRP3

Description

The CSRP3 (cysteine and glycine rich protein 3) is a protein-coding gene located on chromosome 11.

CSRP3, also known as cardiac LIM protein (CLP) or muscle LIM protein (MLP), is a protein encoded by the CSRP3 gene. It is a small protein containing 194 amino acids and is specifically expressed in skeletal and cardiac muscle. In rodents, CSRP3 has also been found in neurons. The CSRP3 gene was discovered in rats in 1994 and mapped to chromosome 11p15.1 in humans, spanning a 20kb genomic region organized in 6 exons. Its full-length transcript is 0.8kb, and a splice variant, MLP-b, has been identified. CSRP3 contains two LIM domains (LIM1 and LIM2), each surrounded by glycine-rich regions, separated by over 50 residues. LIM domains facilitate protein-protein interactions. CSRP3 also has a nuclear localization signal and can be acetylated/deacetylated at lysine residue 69. In myocytes, CSRP3 can form dimers, trimers, and tetramers, impacting its interactions, localization, and function.

CSRP3, also known as CLP or MLP, is a positive regulator of myogenesis. It acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and likely MYOG and MYF6. It enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote the formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis. CSRP3 plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. It might be involved in mechanical stretch sensing and acts as a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. CSRP3 is essential for calcineurin anchorage to the Z line and is required for stress-induced calcineurin-NFAT activation. The role of CSRP3 in the regulation of cytoskeleton dynamics by association with CFL2 is reported to be complex. CSRP3 has been shown to enhance CFL2-mediated F-actin depolymerization depending on the CSRP3:CFL2 molecular ratio, while also reducing the ability of CLF1 and CFL2 to enhance actin depolymerization. CSRP3 is proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. CSRP3 can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity, and protect them from dilution- and cofilin-mediated depolymerization. This function appears to involve its self-association. In vitro, CSRP3 can inhibit PKC/PRKCA activity and is proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling.

CSRP3 is also known as CLP, CMD1M, CMH12, CRP3, LMO4, MLP.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing