View source for Actinin alpha 3

{{Infobox_gene}}
'''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]].<ref name="entrez">{{cite web | title = Entrez Gene: ACTN3 actinin, alpha 3| url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=89| accessdate = }}</ref><ref name="pmid1339456">{{cite journal | vauthors = Beggs AH, Byers TJ, Knoll JH, Boyce FM, Bruns GA, Kunkel LM | title = Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11 | journal = J. Biol. Chem. | volume = 267 | issue = 13 | pages = 9281–8 |date=May 1992 | pmid = 1339456 | doi = | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1339456 | issn = }}</ref>

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 [[Sarcomere#Bands|Z-disc]] and analogous dense bodies, where it helps to anchor the myofibrillar actin filaments.<ref name="entrez" />

== 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 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 ==

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.

== rs1815739  mutation ==

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.<ref name=Epstein>David Epstein. The Sports Gene: Inside the Science of Extraordinary Athletic Performance. {{ISBN|9781101622636}}</ref><ref name="pmid10192379">{{cite journal | vauthors = North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH | title = A common nonsense mutation results in alpha-actinin-3 deficiency in the general population | journal = Nat. Genet. | volume = 21 | issue = 4 | pages = 353–4 |date=April 1999 | pmid = 10192379 | doi = 10.1038/7675 | url = | issn = }}</ref> 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 speculate that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.<ref name=Epstein/>{{rp|155–156}}

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.<ref name="pmid12879365">{{cite journal | vauthors = Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K | title = ACTN3 genotype is associated with human elite athletic performance | journal = Am. J. Hum. Genet. | volume = 73 | issue = 3 | pages = 627–31 |date=September 2003 | pmid = 12879365 | pmc = 1180686 | doi = 10.1086/377590 | url = | issn = }}</ref><ref name="pmid15886711">{{cite journal | vauthors = Niemi AK, Majamaa K | title = Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes | journal = Eur. J. Hum. Genet. | volume = 13 | issue = 8 | pages = 965–9 |date=August 2005 | pmid = 15886711 | doi = 10.1038/sj.ejhg.5201438 | url = | issn = }}</ref><ref name="pmid17033684">{{cite journal | vauthors = Moran CN, Yang N, Bailey ME, Tsiokanos A, Jamurtas A, MacArthur DG, North K, Pitsiladis YP, Wilson RH | title = Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks | journal = Eur. J. Hum. Genet. | volume = 15 | issue = 1 | pages = 88–93 |date=January 2007 | pmid = 17033684 | doi = 10.1038/sj.ejhg.5201724 | url = | issn = }}</ref><ref name="pmid18043716">{{cite journal | vauthors = Roth SM, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF | title = The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes | journal = Eur. J. Hum. Genet. | volume = 16 | issue = 3 | pages = 391–4 |date=March 2008 | pmid = 18043716 | doi = 10.1038/sj.ejhg.5201964 | url = | issn = | pmc = 2668151 }}</ref><ref name="pmid17879893">{{cite journal | vauthors = Papadimitriou ID, Papadopoulos C, Kouvatsi A, Triantaphyllidis C | title = The ACTN3 gene in elite Greek track and field athletes | journal = Int J Sports Med | volume = 29 | issue = 4 | pages = 352–5 |date=April 2008 | pmid = 17879893 | doi = 10.1055/s-2007-965339 | url = | issn = }}</ref>

==Interactions==
ACTN3 has been shown to [[Protein-protein interaction|interact]] with [[Actinin, alpha 2]].<ref name="pmid9675099">{{cite journal | vauthors = Chan Y, Tong HQ, Beggs AH, Kunkel LM | title = Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo | journal = Biochem. Biophys. Res. Commun. | volume = 248 | issue = 1 | pages = 134–9 |date=July 1998 | pmid = 9675099 | doi = 10.1006/bbrc.1998.8920| url = | issn = }}</ref>

==See also==
* [[Actinin]]

==References==
{{reflist|30em}}

==External links==
* {{UCSC gene info|ACTN3}}

==Further reading==
{{refbegin | 2}}
*{{cite journal  | vauthors=MacArthur DG, North KN |title=A gene for speed? The evolution and function of alpha-actinin-3. |journal=BioEssays |volume=26 |issue= 7 |pages= 786–95|year= 2004 |pmid= 15221860 |doi= 10.1002/bies.20061 }}
*{{cite journal  | vauthors=Beggs AH, Byers TJ, Knoll JH |title=Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. |journal=J. Biol. Chem. |volume=267 |issue= 13 |pages= 9281–8 |year= 1992 |pmid= 1339456 |doi=  |display-authors=etal}}
*{{cite journal  | vauthors=Yürüker B, Niggli V |title=Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network.  | series=101|journal=J. Cell Sci. |volume=( Pt 2) |issue=  |pages= 403–14 |year= 1992 |pmid= 1629252 |doi=  }}
*{{cite journal  | vauthors=Pavalko FM, LaRoche SM |title=Activation of human neutrophils induces an interaction between the integrin beta 2-subunit (CD18) and the actin binding protein alpha-actinin. |journal=J. Immunol. |volume=151 |issue= 7 |pages= 3795–807 |year= 1993 |pmid= 8104223 |doi=  }}
*{{cite journal  | vauthors=Chan Y, Tong HQ, Beggs AH, Kunkel LM |title=Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo. |journal=Biochem. Biophys. Res. Commun. |volume=248 |issue= 1 |pages= 134–9 |year= 1998 |pmid= 9675099 |doi=10.1006/bbrc.1998.8920  }}
*{{cite journal  | vauthors=North KN, Yang N, Wattanasirichaigoon D |title=A common nonsense mutation results in alpha-actinin-3 deficiency in the general population.|journal=Nat. Genet. |volume=21 |issue= 4 |pages= 353–4 |year= 1999 |pmid= 10192379 |doi= 10.1038/7675 |display-authors=etal}}
*{{cite journal  | vauthors=Nikolopoulos SN, Spengler BA, Kisselbach K |title=The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. |journal=Oncogene |volume=19 |issue= 3 |pages= 380–6 |year= 2000 |pmid= 10656685 |doi= 10.1038/sj.onc.1203310 |display-authors=etal}}
*{{cite journal  | vauthors=Takada F, Vander Woude DL, Tong HQ |title=Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.|journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 4 |pages= 1595–600 |year= 2001 |pmid= 11171996 |doi= 10.1073/pnas.041609698  | pmc=29302 |display-authors=etal}}
*{{cite journal  | vauthors=Bang ML, Mudry RE, McElhinny AS |title=Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. |journal=J. Cell Biol. |volume=153 |issue= 2 |pages= 413–27 |year= 2001 |pmid= 11309420 |doi=  10.1083/jcb.153.2.413| pmc=2169455  |display-authors=etal}}
*{{cite journal  | vauthors=Mills M, Yang N, Weinberger R |title=Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. |journal=Hum. Mol. Genet. |volume=10 |issue= 13 |pages= 1335–46 |year= 2001 |pmid= 11440986 |doi=10.1093/hmg/10.13.1335  |display-authors=etal}}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | vauthors=Burgueño J, Blake DJ, Benson MA |title=The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin. |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 37545–52 |year= 2003 |pmid= 12837758 |doi= 10.1074/jbc.M302809200 |display-authors=etal}}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 |display-authors=etal}}
*{{cite journal  | vauthors=Clarkson PM, Devaney JM, Gordish-Dressman H |title=ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. |journal=J. Appl. Physiol. |volume=99 |issue= 1 |pages= 154–63 |year= 2005 |pmid= 15718405 |doi= 10.1152/japplphysiol.01139.2004 |display-authors=etal}}
*{{cite journal  | vauthors=Franzot G, Sjöblom B, Gautel M, Djinović Carugo K |title=The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin. |journal=J. Mol. Biol. |volume=348 |issue= 1 |pages= 151–65 |year= 2005 |pmid= 15808860 |doi= 10.1016/j.jmb.2005.01.002 }}
*{{cite journal  | vauthors=Clarkson PM, Hoffman EP, Zambraski E |title=ACTN3 and MLCK genotype associations with exertional muscle damage. |journal=J. Appl. Physiol.|volume=99 |issue= 2 |pages= 564–9 |year= 2005 |pmid= 15817725 |doi= 10.1152/japplphysiol.00130.2005 |display-authors=etal}}
*{{cite journal  | vauthors=Asanuma K, Kim K, Oh J |title=Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner.|journal=J. Clin. Invest. |volume=115 |issue= 5 |pages= 1188–98 |year= 2005 |pmid= 15841212 |doi= 10.1172/JCI23371  | pmc=1070637 |display-authors=etal}}
*{{cite journal  | vauthors=Niemi AK, Majamaa K |title=Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. |journal=Eur. J. Hum. Genet.|volume=13 |issue= 8 |pages= 965–9 |year= 2005 |pmid= 15886711 |doi= 10.1038/sj.ejhg.5201438 }}
*{{cite journal  | vauthors=Triplett JW, Pavalko FM |title=Disruption of alpha-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis.|journal=Am. J. Physiol., Cell Physiol. |volume=291 |issue= 5 |pages= C909–21 |year= 2006 |pmid= 16807302 |doi= 10.1152/ajpcell.00113.2006 }}
{{refend}}

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{{Cytoskeletal Proteins}}

[[Category:Genes on human chromosome 11]]
[[Category:EF-hand-containing proteins]]