ACTA1

SECTIONS

1 - Function
2 - Involvement in disease
3 - Post-translational modifications
4 - Sequence similarities
5 - Cellular localization
6 - Alternative names
7 - Database links
8 - Target type
9 - Primary research area
10 - Molecular weight

Function

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Involvement in disease

Congenital myopathy 2A, typical, autosomal dominant

CMYO2A

A muscular disorder characterized by generalized muscle weakness, delayed motor milestones, hypotonia, and muscle fiber abnormalities on histologic examination. Histologic findings include abnormal thread- or rod-like structures (nemaline rods), intranuclear rods, clumped filaments, cores, or fiber-type disproportion. The spectrum of clinical phenotypes ranges from severe neonatal presentations to onset of a milder disorder in childhood.

None

The disease is caused by variants affecting the gene represented in this entry.

Congenital myopathy 2B, severe infantile, autosomal recessive

CMYO2B

An autosomal recessive skeletal muscle disorder characterized by severe hypotonia with lack of spontaneous movements and respiratory insufficiency, usually leading to death in infancy or early childhood. Longer survival has been reported.

None

The disease is caused by variants affecting the gene represented in this entry.

Congenital myopathy 2C, severe infantile, autosomal dominant

CMYO2C

An autosomal dominant skeletal muscle disorder characterized by severe congenital weakness usually resulting in death from respiratory failure in the first year or so of life. Patients present at birth with hypotonia, lack of antigravity movements, poor head control, and difficulties feeding or breathing, often requiring tube-feeding and mechanical ventilation. Decreased fetal movements may be observed in some cases.

None

The disease is caused by variants affecting the gene represented in this entry.

Myopathy, scapulohumeroperoneal

SHPM

An autosomal dominant muscular disorder characterized by progressive muscle weakness with initial scapulo-humeral-peroneal and distal distribution. Over time, muscle weakness progresses to proximal muscle groups. Clinical characteristics include scapular winging, mild lower facial weakness, foot drop due to foot eversion and dorsiflexion weakness, and selective muscle atrophy. Age at onset and disease progression are variable.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.

Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.

Actin, alpha skeletal muscle, intermediate form

N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.

Methylated at His-75 by SETD3.

(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).