Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''ACTN3''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

(named sprinter gene, speed gene or athlete gene) located on

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

11. All people have two copies (alleles) of this gene. Alpha-actinin is an

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 ...

-binding protein with multiple roles in different cell types. This gene expression is limited to skeletal muscle. It is localized to the Z-disc and analogous dense bodies, where it helps to anchor the myofibrillar actin filaments.

Fast versus slow twitch muscle fibers

Skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

is composed of long cylindrical cells called muscle fibers. There are two types of muscle fibers, slow twitch or

muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in musc ...

(type I) and fast twitch (type II). Slow twitch fibers are more efficient in using oxygen to generate energy, while fast twitch fibers are less efficient. However, fast twitch fibers fire more rapidly, allowing them to generate more power than slow twitch (type I) fibers. Fast twitch fibers and slow twitch fibers are also called white muscle fibers and red muscles fibers, respectively. The alpha-actinin-3 protein is found in type II muscle fibers.

Alleles

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

(rs1815739; 577X) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin-3 in the individuals. The X

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

(ACTN3 577XX) is caused by a C to T transition in

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

16 of the ''ACTN3''

, which causes a transformation of an arginine base (R) to a premature

stop codon In molecular biology, a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the additio ...

(X) resulting in the rs1815739

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

causing no production of the alpha-actinin 3 protein in muscle fibers. The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers. It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world. Over 75% of the persons have one or two copies of ACTN3 577R and have alpha-actinin-3. Homozygous individuals (ACTN3 577XX) have no alpha-actinin-3 (16%-20% of the population), but they have a high level of alpha-actinin-2.

Athletes

There is an association between the ''ACTN3'' R577X polymorphism in sprint and powerlifting performance at an elite level (RR and RX variants are better), and appears to be an association with exercise recovery and lower injury risk. It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.

Interactions

ACTN3 has been shown to interact with alpha-actinin-2.

References

External links

* {{Cytoskeletal Proteins Genes on human chromosome 11 EF-hand-containing proteins