Actinin alpha 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.[3][4]

ACTN3
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1TJT, 1WKU, 3LUE
Identifiers
Aliases	ACTN3, actinin alpha 3 (gene/pseudogene), ACTN3D, actinin alpha 3
External IDs	OMIM: 102574 GeneCards: ACTN3
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.2 Start 66,546,395 bp[1] End 66,563,334 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • calcium ion binding • protein homodimerization activity • ion channel binding • metal ion binding • integrin binding • GO:0001948 protein binding • actin binding • structural constituent of muscle Cellular component • cytosol • pseudopodia • focal adhesion • intracellular • actin filament • extracellular exosome Biological process • regulation of apoptotic process • regulation of aerobic respiration • negative regulation of glycolytic process • negative regulation of calcineurin-NFAT signaling cascade • transition between fast and slow fiber • positive regulation of glucose catabolic process to lactate via pyruvate • focal adhesion assembly • muscle filament sliding • skeletal muscle atrophy • response to denervation involved in regulation of muscle adaptation • negative regulation of oxidative phosphorylation • positive regulation of skeletal muscle tissue growth • regulation of the force of skeletal muscle contraction • negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	n/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.[3]

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.[5][6] 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.[7] The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers.[7]

It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.[5]^:155–156

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.[7] It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.[7]

Interactions

ACTN3 has been shown to interact with Actinin, alpha 2.[8]

See also

• Actinin

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. "Entrez Gene: ACTN3 actinin, alpha 3".
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): 9281–8. PMID 1339456.
5. David Epstein. The Sports Gene: Inside the Science of Extraordinary Athletic Performance. ISBN 9781101622636
6. 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): 353–4. doi:10.1038/7675. PMID 10192379.
7. 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.
8. 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): 134–9. doi:10.1006/bbrc.1998.8920. PMID 9675099.

Further reading

• MacArthur DG, North KN (July 2004). "A gene for speed? The evolution and function of alpha-actinin-3". BioEssays. 26 (7): 786–95. doi:10.1002/bies.20061. PMID 15221860.
• 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): 9281–8. PMID 1339456.
• Yürüker B, Niggli V (February 1992). "Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network". Journal of Cell Science. 101. 101 ( Pt 2): 403–14. PMID 1629252.
• Pavalko FM, LaRoche SM (October 1993). "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. PMID 8104223.
• 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): 134–9. doi:10.1006/bbrc.1998.8920. PMID 9675099.
• 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): 353–4. doi:10.1038/7675. PMID 10192379.
• Nikolopoulos SN, Spengler BA, Kisselbach K, Evans AE, Biedler JL, Ross RA (January 2000). "The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells". Oncogene. 19 (3): 380–6. doi:10.1038/sj.onc.1203310. PMID 10656685.
• Takada F, Vander Woude DL, Tong HQ, Thompson TG, Watkins SC, Kunkel LM, Beggs AH (February 2001). "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. doi:10.1073/pnas.041609698. PMC 29302. PMID 11171996.
• Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S (April 2001). "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. doi:10.1083/jcb.153.2.413. PMC 2169455. PMID 11309420.
• Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K (June 2001). "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. doi:10.1093/hmg/10.13.1335. PMID 11440986.
• Burgueño J, Blake DJ, Benson MA, Tinsley CL, Esapa CT, Canela EI, Penela P, Mallol J, Mayor F, Lluis C, Franco R, Ciruela F (September 2003). "The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin". The Journal of Biological Chemistry. 278 (39): 37545–52. doi:10.1074/jbc.M302809200. PMID 12837758.
• Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Hoffman EP (July 2005). "ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women". Journal of Applied Physiology. 99 (1): 154–63. doi:10.1152/japplphysiol.01139.2004. PMID 15718405.
• Franzot G, Sjöblom B, Gautel M, Djinović Carugo K (April 2005). "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. doi:10.1016/j.jmb.2005.01.002. PMID 15808860.
• Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, Harmon B, Devaney JM (August 2005). "ACTN3 and MLCK genotype associations with exertional muscle damage". Journal of Applied Physiology. 99 (2): 564–9. doi:10.1152/japplphysiol.00130.2005. PMID 15817725.
• Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, Reiser J, Mundel P (May 2005). "Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner". The Journal of Clinical Investigation. 115 (5): 1188–98. doi:10.1172/JCI23371. PMC 1070637. PMID 15841212.
• Niemi AK, Majamaa K (August 2005). "Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes". European Journal of Human Genetics. 13 (8): 965–9. doi:10.1038/sj.ejhg.5201438. PMID 15886711.
• Triplett JW, Pavalko FM (November 2006). "Disruption of alpha-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis". American Journal of Physiology. Cell Physiology. 291 (5): C909–21. doi:10.1152/ajpcell.00113.2006. PMID 16807302.

External links

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