Biology:Actinin alpha 3

Generic protein structure example

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.

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.

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.

Alleles

An allele (rs1815739; R577X) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin 3 in a significant proportion of the population. The X homozygous genotype 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. 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.

Athletes

There is an association between the ACTN3 R577X polymorphism in sprint and powerlifting performance at an elite level, 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 Actinin, alpha 2.

See also

• Actinin

Further reading

• "A gene for speed? The evolution and function of alpha-actinin-3". BioEssays 26 (7): 786–95. July 2004. doi:10.1002/bies.20061. PMID 15221860. 
• "Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11". The Journal of Biological Chemistry 267 (13): 9281–8. May 1992. doi:10.1016/S0021-9258(19)50420-3. PMID 1339456. 
• "Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network". Journal of Cell Science. 101 101 ( Pt 2) (2): 403–14. February 1992. doi:10.1242/jcs.101.2.403. PMID 1629252. 
• "Activation of human neutrophils induces an interaction between the integrin beta 2-subunit (CD18) and the actin binding protein alpha-actinin". Journal of Immunology 151 (7): 3795–807. October 1993. PMID 8104223. 
• "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): 134–9. July 1998. doi:10.1006/bbrc.1998.8920. PMID 9675099. 
• "A common nonsense mutation results in alpha-actinin-3 deficiency in the general population". Nature Genetics 21 (4): 353–4. April 1999. doi:10.1038/7675. PMID 10192379. 
• "The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells". Oncogene 19 (3): 380–6. January 2000. doi:10.1038/sj.onc.1203310. PMID 10656685. 
• "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines". Proceedings of the National Academy of Sciences of the United States of America 98 (4): 1595–600. February 2001. doi:10.1073/pnas.041609698. PMID 11171996. 
• "Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies". The Journal of Cell Biology 153 (2): 413–27. April 2001. doi:10.1083/jcb.153.2.413. PMID 11309420. 
• "Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy". Human Molecular Genetics 10 (13): 1335–46. June 2001. doi:10.1093/hmg/10.13.1335. PMID 11440986. 
• "The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin". The Journal of Biological Chemistry 278 (39): 37545–52. September 2003. doi:10.1074/jbc.M302809200. PMID 12837758. 
• "ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women". Journal of Applied Physiology 99 (1): 154–63. July 2005. doi:10.1152/japplphysiol.01139.2004. PMID 15718405. 
• "The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin". Journal of Molecular Biology 348 (1): 151–65. April 2005. doi:10.1016/j.jmb.2005.01.002. PMID 15808860. 
• "ACTN3 and MLCK genotype associations with exertional muscle damage". Journal of Applied Physiology 99 (2): 564–9. August 2005. doi:10.1152/japplphysiol.00130.2005. PMID 15817725. 
• "Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner". The Journal of Clinical Investigation 115 (5): 1188–98. May 2005. doi:10.1172/JCI23371. PMID 15841212. 
• "Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes". European Journal of Human Genetics 13 (8): 965–9. August 2005. doi:10.1038/sj.ejhg.5201438. PMID 15886711. 
• "Disruption of alpha-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis". American Journal of Physiology. Cell Physiology 291 (5): C909–21. November 2006. doi:10.1152/ajpcell.00113.2006. PMID 16807302. 

External links

• Human ACTN3 genome location and ACTN3 gene details page in the UCSC Genome Browser.