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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

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

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 b ...

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

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

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 ov ...

-binding protein with multiple roles in different cell types. This gene expression is limited to skeletal muscle. It is localized to the

Z-disc 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 ...

and analogous dense bodies, where it helps to anchor the myofibrillar actin filaments.

Fast versus slow twitch muscle fibers

Skeletal muscle 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-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...

(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 (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

(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. Mo ...

genotype (ACTN3 577XX) is caused by a C to T transition in exon 16 of the ''ACTN3''

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

stop codon In molecular biology (specifically protein biosynthesis), 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 mess ...

(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 replication, DNA or viral repl ...

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 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 ...

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 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 alpha-actinin-2.

References

External links

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