ACTN3

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Actinin, alpha 3

PDB rendering based on 1tjt.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ACTN3 ; MGC117002; MGC117005
External IDs OMIM102574 MGI99678 HomoloGene862 GeneCards: ACTN3 Gene
RNA expression pattern
PBB GE ACTN3 206891 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 89 11474
Ensembl ENSG00000248746 ENSMUSG00000006457
UniProt Q08043 O88990
RefSeq (mRNA) NM_001104 NM_013456.1
RefSeq (protein) NP_001095 NP_038484.1
Location (UCSC) Chr 11:
66.31 – 66.33 Mb
Chr 19:
4.86 – 4.88 Mb
PubMed search [1] [2]

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.[1][2]

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.[1]

Fast versus slow twitch muscle fibers[edit]

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 and generate more force. Fast twitch fibers and slow twitch fibers are also called white muscle fibers and red muscles fibers, respectively.

ACTN3 in muscle fiber[edit]

Each muscle fiber is composed of long tubes called myofibrils which in turn are composed of filaments. There are two types of filaments: actin (thin filaments) and myosin (thick filaments) which are arranged in parallel. A muscle contraction involves these filaments sliding past each other.

Actin filaments are stabilized by actin binding proteins known as actinins of which there are two main types, type 2 and type 3. Each of these is encoded by a specific gene, ACTN2 and ACTN3 respectively.

ACTN2 is expressed in all skeletal muscle fibers whereas ACTN3 is expressed only in fast twitch fibers.

The rs1815739 mutation[edit]

A mutation (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.[3] Based on ethnicity the deficiency is found in 20-50% of people. Generally, Africans have the lowest incidence of the mutation while Asians have the highest. Scientists believe that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.

Studies have linked the fiber twitch type with ACTN3, i.e. fast twitch fiber abundant individuals carry the non-mutant gene version. Also, studies in elite athletes have shown that the ACTN3 gene may influence athletic performance. While the non-mutant version of the gene is associated with sprint performance, the mutant version is associated with endurance.[4][5][6][7][8]

Interactions[edit]

ACTN3 has been shown to interact with Actinin, alpha 2.[9]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: ACTN3 actinin, alpha 3". 
  2. ^ 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". J. Biol. Chem. 267 (13): 9281–8. PMID 1339456. 
  3. ^ 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". Nat. Genet. 21 (4): 353–4. doi:10.1038/7675. PMID 10192379. 
  4. ^ Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K (September 2003). "ACTN3 genotype is associated with human elite athletic performance". Am. J. Hum. Genet. 73 (3): 627–31. doi:10.1086/377590. PMC 1180686. PMID 12879365. 
  5. ^ Niemi AK, Majamaa K (August 2005). "Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes". Eur. J. Hum. Genet. 13 (8): 965–9. doi:10.1038/sj.ejhg.5201438. PMID 15886711. 
  6. ^ Moran CN, Yang N, Bailey ME, Tsiokanos A, Jamurtas A, MacArthur DG, North K, Pitsiladis YP, Wilson RH (January 2007). "Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks". Eur. J. Hum. Genet. 15 (1): 88–93. doi:10.1038/sj.ejhg.5201724. PMID 17033684. 
  7. ^ Roth SM, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF (March 2008). "The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes". Eur. J. Hum. Genet. 16 (3): 391–4. doi:10.1038/sj.ejhg.5201964. PMC 2668151. PMID 18043716. 
  8. ^ Papadimitriou ID, Papadopoulos C, Kouvatsi A, Triantaphyllidis C (April 2008). "The ACTN3 gene in elite Greek track and field athletes". Int J Sports Med 29 (4): 352–5. doi:10.1055/s-2007-965339. PMID 17879893. 
  9. ^ 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". Biochem. Biophys. Res. Commun. 248 (1): 134–9. doi:10.1006/bbrc.1998.8920. PMID 9675099. 

Further reading[edit]