Actinin alpha 3: Difference between revisions

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'''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-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| access-date = }}</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 = The Journal of Biological Chemistry | volume = 267 | issue = 13 | pages = 9281–8 | date = May 1992 | pmid = 1339456 | doi = | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1339456 }}</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" />
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 ==
== 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.
[[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.


== ACTN3 in muscle fiber ==
==Alleles ==


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.
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.<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 = Nature Genetics | volume = 21 | issue = 4 | pages = 353–4 | date = April 1999 | pmid = 10192379 | doi = 10.1038/7675 }}</ref> The X [[Zygosity|homozygous]] [[genotype]] is caused by a C to T transition in [[exon]] 16 of the ''ACTN3'' [[gene]], which causes a transformation of an [[Arginine|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.<ref name=":0">{{cite journal | vauthors = Pickering C, Kiely J | title = ACTN3: More than Just a Gene for Speed | journal = Frontiers in Physiology | volume = 8 | pages = 1080 | date = 2017 | pmid = 29326606 | pmc = 5741991 | doi = 10.3389/fphys.2017.01080 }}</ref> The 577XX [[Polymorphism (biology)|polymorphism]] causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers.<ref name=":0" />


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.
It has been speculated 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}}


ACTN2 is expressed in all skeletal muscle fibers whereas ACTN3 is expressed only in fast twitch fibers.
=== Athletes ===
There is an association between the ''ACTN3'' R577X [[Polymorphism (biology)|polymorphism]] in sprint and powerlifting performance at an elite level, and appears to be an association with exercise recovery and lower injury risk.<ref name=":0" />  It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.<ref name=":0" />


== rs1815739  mutation ==
== Interactions ==


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}}
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 = Biochemical and Biophysical Research Communications | volume = 248 | issue = 1 | pages = 134–9 | date = July 1998 | pmid = 9675099 | doi = 10.1006/bbrc.1998.8920 }}</ref>


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>
== See also ==
 
==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]]
* [[Actinin]]


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


==External links==
== Further reading ==
{{refbegin}}
* {{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 | date = July 2004 | pmid = 15221860 | doi = 10.1002/bies.20061 }}
* {{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 = The Journal of Biological Chemistry | volume = 267 | issue = 13 | pages = 9281–8 | date = May 1992 | pmid = 1339456 | doi =  }}
* {{cite journal | vauthors = Yürüker B, Niggli V | title = Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network | journal = Journal of Cell Science | volume = 101 ( Pt 2) | issue =  | pages = 403–14 | date = February 1992 | pmid = 1629252 | doi =  | series = 101 }}
* {{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 = Journal of Immunology | volume = 151 | issue = 7 | pages = 3795–807 | date = October 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 = Biochemical and Biophysical Research Communications | volume = 248 | issue = 1 | pages = 134–9 | date = July 1998 | pmid = 9675099 | doi = 10.1006/bbrc.1998.8920 }}
* {{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 = Nature Genetics | volume = 21 | issue = 4 | pages = 353–4 | date = April 1999 | pmid = 10192379 | doi = 10.1038/7675 }}
* {{cite journal | vauthors = Nikolopoulos SN, Spengler BA, Kisselbach K, Evans AE, Biedler JL, Ross RA | 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 | date = January 2000 | pmid = 10656685 | doi = 10.1038/sj.onc.1203310 }}
* {{cite journal | vauthors = Takada F, Vander Woude DL, Tong HQ, Thompson TG, Watkins SC, Kunkel LM, Beggs AH | title = Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 4 | pages = 1595–600 | date = February 2001 | pmid = 11171996 | pmc = 29302 | doi = 10.1073/pnas.041609698 }}
* {{cite journal | vauthors = Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S | title = Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies | journal = The Journal of Cell Biology | volume = 153 | issue = 2 | pages = 413–27 | date = April 2001 | pmid = 11309420 | pmc = 2169455 | doi = 10.1083/jcb.153.2.413 }}
* {{cite journal | vauthors = Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K | title = Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy | journal = Human Molecular Genetics | volume = 10 | issue = 13 | pages = 1335–46 | date = June 2001 | pmid = 11440986 | doi = 10.1093/hmg/10.13.1335 }}
* {{cite journal | vauthors = Burgueño J, Blake DJ, Benson MA, Tinsley CL, Esapa CT, Canela EI, Penela P, Mallol J, Mayor F, Lluis C, Franco R, Ciruela F | title = The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 39 | pages = 37545–52 | date = September 2003 | pmid = 12837758 | doi = 10.1074/jbc.M302809200 }}
* {{cite journal | vauthors = 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 | title = ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women | journal = Journal of Applied Physiology | volume = 99 | issue = 1 | pages = 154–63 | date = July 2005 | pmid = 15718405 | doi = 10.1152/japplphysiol.01139.2004 }}
* {{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 = Journal of Molecular Biology | volume = 348 | issue = 1 | pages = 151–65 | date = April 2005 | pmid = 15808860 | doi = 10.1016/j.jmb.2005.01.002 }}
* {{cite journal | vauthors = Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, Harmon B, Devaney JM | title = ACTN3 and MLCK genotype associations with exertional muscle damage | journal = Journal of Applied Physiology | volume = 99 | issue = 2 | pages = 564–9 | date = August 2005 | pmid = 15817725 | doi = 10.1152/japplphysiol.00130.2005 }}
* {{cite journal | vauthors = Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, Reiser J, Mundel P | title = Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner | journal = The Journal of Clinical Investigation | volume = 115 | issue = 5 | pages = 1188–98 | date = May 2005 | pmid = 15841212 | pmc = 1070637 | doi = 10.1172/JCI23371 }}
* {{cite journal | vauthors = Niemi AK, Majamaa K | title = Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes | journal = European Journal of Human Genetics | volume = 13 | issue = 8 | pages = 965–9 | date = August 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 = American Journal of Physiology. Cell Physiology | volume = 291 | issue = 5 | pages = C909-21 | date = November 2006 | pmid = 16807302 | doi = 10.1152/ajpcell.00113.2006 }}
{{refend}}
 
== External links ==
* {{UCSC gene info|ACTN3}}
* {{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}}


{{PDB Gallery|geneid=89}}
{{PDB Gallery|geneid=89}}

Latest revision as of 15:24, 19 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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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

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.[3][4] 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.[5] The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers.[5]

It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.[3]: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.[5] It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery.[5]

Interactions

ACTN3 has been shown to interact with Actinin, alpha 2.[6]

See also

References

  1. ↑ 1.0 1.1 "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". The Journal of Biological Chemistry. 267 (13): 9281–8. PMID 1339456.
  3. ↑ 3.0 3.1 David Epstein. The Sports Gene: Inside the Science of Extraordinary Athletic Performance. ISBN 9781101622636
  4. ↑ 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.
  5. ↑ 5.0 5.1 5.2 5.3 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.
  6. ↑ 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

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