Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''FLNC''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
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
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
filamentous actin-binding domain, followed by a lengthy
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
self-association domain containing a series of
immunoglobulin
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
-like domains, and a membrane
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
-binding domain.
Filamin-C interacts with
γ-sarcoglycan and
δ-sarcoglycan at the sarcolemma;
and
FATZ/calsarcin/myozenin at Z-lines,
as well as
LL5β.
Filamin-C has also been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
INPPL1
SH2-domain containing Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 is an enzyme that in humans is encoded by the ''INPPL1'' gene.
INPPL1 encodes inositol polyphosphate-5 phosphatase-like 1, a protein that in addition to the phosphatase ...
,
KCND2
Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the ''KCND2'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase ...
,
and
MAP2K4.
Function
The family of Filamin proteins crosslink
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
. 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
hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
,
restrictive cardiomyopathy
Restrictive cardiomyopathy (RCM) is a form of cardiomyopathy in which the walls of the heart are rigid (but not thickened). Thus the heart is restricted from stretching and filling with blood properly. It is the least common of the three original s ...
and a higher incidence of
sudden cardiac death
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
.
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.
References
Further reading
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External links
Mass spectrometry characterization of human FLNC at COPaKB GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
{{Cytoskeletal proteins