CSRP3

This gene encodes a member of the CSRP family of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this protein is found in a group of proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Mutations in this gene are thought to cause heritable forms of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in humans. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq]

cysteine and glycine-rich protein 3 (cardiac LIM protein)

Positive regulator of myogenesis. Acts as cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity).

Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity).

The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443).

Proposed to contribute to the maintenance of muscle cell integerity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443).

In vitro can inhibit PKC/PRKCA activity (PubMed:27353086).

Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity).

Isoform 2:
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.

Actin cytoskeleton organization Source: GO_Central
Cardiac muscle contraction Source: BHF-UCL
Cardiac muscle hypertrophy Source: BHF-UCL
Cardiac muscle tissue development Source: BHF-UCL
Cardiac myofibril assembly Source: BHF-UCL
Cellular calcium ion homeostasis Source: BHF-UCL
Detection of muscle stretch Source: BHF-UCL
Glucose homeostasis Source: Ensembl
Inflammatory response Source: Ensembl
Insulin receptor signaling pathway Source: Ensembl
Muscle tissue development Source: GO_Central
Negative regulation of actin filament severing Source: MGI
Negative regulation of myoblast differentiation Source: MGI
Positive regulation of actin filament severing Source: MGI
Positive regulation of myoblast differentiation Source: MGI
Positive regulation of transcription by RNA polymerase II Source: MGI
Protein kinase C signaling Source: Ensembl
Protein localization to organelle Source: BHF-UCL
Regulation of protein localization to plasma membrane Source: Ensembl
Regulation of the force of heart contraction Source: BHF-UCL
Sarcomere organization Source: GO_Central
Skeletal muscle tissue development Source: ProtInc
T-tubule organization Source: Ensembl

Cytoskeleton; Cytoplasm; Nucleus; Z line; Sarcomere. Nucleocytoplasmic shuttling protein. Mainly cytoplasmic. In the Z line, found associated with GLRX3 (By similarity).
Isoform 2: Z line

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.
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.

Phosphorylated by PKC/PRKCA.