ACTC1 encodes cardiac muscle alpha actin.
This isoform differs from the alpha actin that is expressed in skeletal muscle,
ACTA1
Actin, alpha skeletal muscle is a protein that in humans is encoded by the ''ACTA1'' gene.
Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved proteins ...
. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart.
Structure
Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids.
Cardiac alpha actin is a filamentous protein extending from a complex mesh with cardiac alpha-actinin (
ACTN2
Alpha-actinin-2 is a protein which in humans is encoded by the ''ACTN2'' gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to ...
) at
Z-lines towards the center of the
sarcomere
A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called musc ...
. Polymerization of globular actin
(G-actin) leads to a structural filament
(F-actin) in the form of a two-stranded
helix
A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...
. Each actin can bind to four others. The atomic structure of monomeric actin was solved by Kabsch et al., and closely thereafter this same group published the structure of the actin filament.
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 ...
s are highly conserved proteins; the alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Cardiac (ACTC1) and skeletal (
ACTA1
Actin, alpha skeletal muscle is a protein that in humans is encoded by the ''ACTA1'' gene.
Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved proteins ...
) alpha actins differ by only four amino acids (
Asp4
Glu,
Glu5
Asp,
Leu301
Met,
Ser
Ser or SER may refer to:
Places
* Ser, a village in Bogdand Commune, Satu Mare County, Romania
* Serpens (Ser), an astronomical constellation of the northern hemisphere
* Serres, known as Ser in Serbian, a city in Macedonia, Greece
Organization ...
360
Thr; cardiac/skeletal). The actin monomer has two asymmetric domains; the larger inner domain comprised by sub-domains 3 and 4, and the smaller outer domain by sub-domains 1 and 2. Both the amino and
carboxy-termini lie in sub-domain 1 of the outer domain.
Function
Actin is a dynamic structure that can adapt two states of flexibility, with the greatest difference between the states occurring as a result of movement within sub-domain 2. Myosin binding increases the flexibility of actin, and cross-linking studies have shown that myosin subfragment-1 binds to actin amino acid residues 48-67 within actin sub-domain 2, which may account for this effect.
It has been suggested that the ''ACTC1'' gene has a role during development. Experiments in chick embryos found an association between ''ACTC1''
knockdown and a reduction in the
atrial septa.
Clinical significance
Polymorphisms in ''ACTC1'' have been linked to
Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...
in a small number of Japanese patients. Further studies in patients from South Africa found no association. The E101K
missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution.
Substitution of protein from DNA mutations
Missense m ...
has been associated with
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 ...
and
Left Ventricular Noncompaction.
Another mutation has in the ''ACTC1'' gene has been associated with
atrial septal defect
Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...
s.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
Mass spectrometry characterization of human ACTC1 at COPaKB GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview*
{{Cytoskeletal proteins
Human proteins