FLNC (gene)

Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a is_associated_with::protein that in humans is encoded by the FLNC is_associated_with::gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.

Structure
Filamin-C is a 290.8 kDa protein composed of 2725 amino acids. Filamin-C, like the ubiquitously-expressed isoform Filamin-A, have an N-terminal filamentous actin-binding domain, followed by a lengthy C-terminal self-association domain containing a series of is_associated_with::immunoglobulin-like domains, and a membrane is_associated_with::glycoprotein-binding domain. Filamin-C interacts with γ-sarcoglycan and δ-sarcoglycan at the sarcolemma; myotilin and FATZ/calsarcin/myozenin at Z-lines,    as well as LL5β. Filamin-C has also been shown to interact with is_associated_with::INPPL1, is_associated_with::KCND2, and is_associated_with::MAP2K4.

Function
The family of Filamin proteins crosslink is_associated_with::actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin is_associated_with::cytoskeleton. However, the precise function of the Filamin-C isoform is still under investigation. As Filamin-C is localized mainly to striated muscle, its functions are likely specific to the specialized sarcomeric cytoskeleton present in muscle. As Filamin-C is found at both subsarcolemmal regions and at Z-lines, one plausible function of Filamin-C would be to act as a mode of communication between the membrane and the sarcomere. In skeletal muscle, Filamin-C is found at sites of core formation in skeletal myopathies, and alterations in subcellular localization of Filamin-C have been exhibited in limb-girdle muscular dystrophy and Duchenne muscular dystrophy.

Clinical significance
Mutations in Filamin C have been associated with human is_associated_with::hypertrophic cardiomyopathy and a higher incidence of is_associated_with::sudden cardiac death. Expression of mutant protein in rat cardiac cells demonstrated that mutant Filamin C forms aggregates, which may provide a mechanistic link to the observed cardiac dysfunction. Deficiency of this protein has been associated with muscle weakness.