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) 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 hel ...
. 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 protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...
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 (
Asp
Asp may refer to:
Places
* Asp, part of Densbüren, Aargau, Switzerland
* Aspe (''Asp'' in Valencian), Alicante, Spain
* Asp Lake, a lake in Minnesota
Animals
* Asp (fish)
* Asp (snake), in antiquity, one of several venomous snakes
** ''Cera ...
4
Glu,
Glu5
Asp
Asp may refer to:
Places
* Asp, part of Densbüren, Aargau, Switzerland
* Aspe (''Asp'' in Valencian), Alicante, Spain
* Asp Lake, a lake in Minnesota
Animals
* Asp (fish)
* Asp (snake), in antiquity, one of several venomous snakes
** ''Cera ...
,
Leu301
Met,
Ser360
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
Knockdown or knock-down may refer to:
* Knockdown, a situation in full-contact combat sports where a fighter is down or vulnerable, often preliminary to a knockout
* "Knockdown" (Castle), the thirteenth episode of the third season of the TV serie ...
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 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 defects.
References
Further reading
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External links
Mass spectrometry characterization of human ACTC1 at COPaKB GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview*
{{Cytoskeletal proteins
Human proteins