Alpha-actinin-3

Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ACTN3 gene (named sprinter gene, speed gene or athlete gene) located on chromosome 11. All people have two copies (alleles) of this gene.[3][4]

ACTN3
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesACTN3, actinin alpha 3 (gene/pseudogene), ACTN3D, actinin alpha 3
External IDsOMIM: 102574 GeneCards: ACTN3
Orthologs
SpeciesHumanMouse
Entrez

89

n/a

Ensembl

ENSG00000248746

n/a

UniProt

Q08043

n/a

RefSeq (mRNA)

NM_001104
NM_001258371

n/a

RefSeq (protein)

NP_001095
NP_001245300

n/a

Location (UCSC)Chr 11: 66.55 – 66.56 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Alpha-actinin is an actin-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.[5]

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 (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

An allele (rs1815739; 577X) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin-3 in the individuals.[6][7] The X homozygous genotype (ACTN3 577XX) is caused by a C to T transition in exon 16 of the ACTN3 gene, which causes a transformation of an arginine base (R) to a premature stop codon (X) resulting in the rs1815739 mutation causing no production of the alpha-actinin 3 protein in muscle fibers.[8] The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers.[8]

It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.[6]: 155–156  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),[9][10] 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.[8] It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.[8]

Interactions

ACTN3 has been shown to interact with alpha-actinin-2.[11]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000248746 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "ACTN3 - Alpha-actinin-3 - Homo sapiens (Human) - ACTN3 gene & protein". www.uniprot.org. Retrieved 22 April 2022.
  4. Beggs AH, Byers TJ, Knoll JH, Boyce FM, Bruns GA, Kunkel LM (May 1992). "Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11". The Journal of Biological Chemistry. 267 (13): 9281–9288. doi:10.1016/S0021-9258(19)50420-3. PMID 1339456.
  5. "Entrez Gene: ACTN3 actinin, alpha 3".
  6. Epstein, David (2013). The Sports Gene: Inside the Science of Extraordinary Athletic Performance. Penguin. ISBN 978-1-101-62263-6.
  7. North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH (April 1999). "A common nonsense mutation results in alpha-actinin-3 deficiency in the general population". Nature Genetics. 21 (4): 353–354. doi:10.1038/7675. PMID 10192379. S2CID 19882092.
  8. Pickering C, Kiely J (2017). "ACTN3: More than Just a Gene for Speed". Frontiers in Physiology. 8: 1080. doi:10.3389/fphys.2017.01080. PMC 5741991. PMID 29326606.
  9. Hogarth MW, Houweling PJ, Thomas KC, Gordish-Dressman H, Bello L, Pegoraro E, et al. (January 2017). "Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy". Nature Communications. 8 (1): 14143. Bibcode:2017NatCo...814143H. doi:10.1038/ncomms14143. PMC 5290331. PMID 28139640.
  10. Seto, Jane T.; Lek, Monkol; Quinlan, Kate G.R.; Houweling, Peter J.; Zheng, Xi F.; Garton, Fleur; MacArthur, Daniel G.; Raftery, Joanna M.; Garvey, Sean M.; Hauser, Michael A.; Yang, Nan; Head, Stewart I.; North, Kathryn N. (2011). "Deficiency of α-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling". Human Molecular Genetics. 20 (15): 2914–2927. doi:10.1093/hmg/ddr196. PMID 21536590. Retrieved 15 February 2022.
  11. Chan Y, Tong HQ, Beggs AH, Kunkel LM (July 1998). "Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo". Biochemical and Biophysical Research Communications. 248 (1): 134–139. doi:10.1006/bbrc.1998.8920. PMID 9675099.

Further reading
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