Actn3

Summary

Gene Symbol: Actn3
Description: actinin alpha 3
Alias: alpha-actinin-3, F-actin cross-linking protein, alpha-actinin skeletal muscle
Species: mouse
Products:     Actn3

Top Publications

  1. Yoon J, Olson E, Arnold H, Wold B. Different MRF4 knockout alleles differentially disrupt Myf-5 expression: cis-regulatory interactions at the MRF4/Myf-5 locus. Dev Biol. 1997;188:349-62 pubmed
    ..cis-acting interactions between Myf-5 and MRF4 may therefore play a significant role in regulating expression of these genes in the early myotomes of wildtype embryos. ..
  2. Zabludoff S, Csete M, Wagner R, Yu X, Wold B. p27Kip1 is expressed transiently in developing myotomes and enhances myogenesis. Cell Growth Differ. 1998;9:1-11 pubmed
    ..At later times, when p27 protein has been down-regulated, it is proposed that accumulation of p18, p21, and p57 maintain the differentiated myocytes in a postmitotic state. ..
  3. Seto J, Lek M, Quinlan K, Houweling P, Zheng X, Garton F, et al. Deficiency of ?-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling. Hum Mol Genet. 2011;20:2914-27 pubmed publisher
    ..Homozygosity for the common null polymorphism (R577X) in ACTN3 results in the absence of fast fiber-specific ?-actinin-3 in ?20% of the general population...
  4. MacArthur D, Seto J, Chan S, Quinlan K, Raftery J, Turner N, et al. An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet. 2008;17:1076-86 pubmed publisher
    A common nonsense polymorphism (R577X) in the ACTN3 gene results in complete deficiency of the fast skeletal muscle fiber protein alpha-actinin-3 in an estimated one billion humans worldwide...
  5. Seto J, Chan S, Turner N, MacArthur D, Raftery J, Berman Y, et al. The effect of ?-actinin-3 deficiency on muscle aging. Exp Gerontol. 2011;46:292-302 pubmed publisher
    ..of the fast-twitch muscle protein ?-actinin-3 due to homozygosity for a nonsense polymorphism (R577X) in the ACTN3 gene is common in humans...
  6. Quinlan K, Seto J, Turner N, Vandebrouck A, Floetenmeyer M, MacArthur D, et al. Alpha-actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle. Hum Mol Genet. 2010;19:1335-46 pubmed publisher
    Approximately one billion people worldwide are homozygous for a stop codon polymorphism in the ACTN3 gene (R577X) which results in complete deficiency of the fast fibre muscle protein alpha-actinin-3...
  7. MacArthur D, Seto J, Raftery J, Quinlan K, Huttley G, Hook J, et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet. 2007;39:1261-5 pubmed
    ..muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene...
  8. Chan S, Seto J, Houweling P, Yang N, North K, Head S. Properties of extensor digitorum longus muscle and skinned fibers from adult and aged male and female Actn3 knockout mice. Muscle Nerve. 2011;43:37-48 pubmed publisher
    Absence of ?-actinin-3, encoded by the ACTN3 "speed gene," is associated with poorer sprinting performance in athletes and a slowing of relaxation in fast-twitch muscles of Actn3 knockout (KO) mice...
  9. Burgueno J, Blake D, Benson M, Tinsley C, Esapa C, Canela E, et al. The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin. J Biol Chem. 2003;278:37545-52 pubmed
    ..These findings suggest an alpha-actinin-dependent association between the actin cytoskeleton and A2AR trafficking. ..

More Information

Publications37

  1. Hogarth M, Garton F, Houweling P, Tukiainen T, Lek M, MacArthur D, et al. Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion. Hum Mol Genet. 2016;25:866-77 pubmed publisher
    A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼ 18% of the global population...
  2. Keicher C, Gambaryan S, Schulze E, Marcus K, Meyer H, Butt E. Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase. Biochem Biophys Res Commun. 2004;324:308-16 pubmed
    ..Immunoblotting of LASP-1 in various mouse and human tissues detected a similar prominent expression in non-muscle tissue. Altogether, our data suggest so far no functional differences between human and mouse LASP-1. ..
  3. Head S, Chan S, Houweling P, Quinlan K, Murphy R, Wagner S, et al. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution. PLoS Genet. 2015;11:e1004862 pubmed publisher
    ..muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3 gene...
  4. Cohen S, Zhai B, Gygi S, Goldberg A. Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy. J Cell Biol. 2012;198:575-89 pubmed publisher
    ..Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments...
  5. Itoh S, Ding B, Shishido T, Lerner Marmarosh N, Wang N, Maekawa N, et al. Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in ischemic and diabetic myocardium. Circulation. 2006;113:1787-98 pubmed
  6. Seto J, Quinlan K, Lek M, Zheng X, Garton F, MacArthur D, et al. ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest. 2013;123:4255-63 pubmed publisher
    ..occurs in approximately 16% of the global population due to homozygosity for a common nonsense polymorphism in the ACTN3 gene...
  7. Palmer S, Groves N, Schindeler A, Yeoh T, Biben C, Wang C, et al. The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner. J Cell Biol. 2001;153:985-98 pubmed
  8. Collin G, Marshall J, King B, Milan G, Maffei P, Jagger D, et al. The Alström syndrome protein, ALMS1, interacts with ?-actinin and components of the endosome recycling pathway. PLoS ONE. 2012;7:e37925 pubmed publisher
    ..Our results suggest a role for ALMS1 variants in the recycling endosome pathway and give us new insights into the pathogenesis of a subset of clinical phenotypes associated with ALMS. ..
  9. Lu S, Carroll S, Herrera A, Ozanne B, Horowits R. New N-RAP-binding partners alpha-actinin, filamin and Krp1 detected by yeast two-hybrid screening: implications for myofibril assembly. J Cell Sci. 2003;116:2169-78 pubmed
    ..The results suggest that sequential recruitment of N-RAP binding partners may serve an important role during myofibril assembly. ..
  10. Lee F, Houweling P, North K, Quinlan K. How does α-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the 'gene for speed'. Biochim Biophys Acta. 2016;1863:686-93 pubmed publisher
    ..people worldwide are deficient in the skeletal muscle protein α-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism...
  11. Dixson J, Forstner M, Garcia D. The alpha-actinin gene family: a revised classification. J Mol Evol. 2003;56:1-10 pubmed
    ..In addition, the topology found for this gene family undermines the 2R hypothesis theory of two rounds of genome duplication early in vertebrate evolution. ..
  12. Frey N, Richardson J, Olson E. Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. Proc Natl Acad Sci U S A. 2000;97:14632-7 pubmed
    ..Calsarcins represent a novel family of sarcomeric proteins that link calcineurin with the contractile apparatus, thereby potentially coupling muscle activity to calcineurin activation. ..
  13. Gokhin D, Lewis R, McKeown C, Nowak R, Kim N, Littlefield R, et al. Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology. J Cell Biol. 2010;189:95-109 pubmed publisher
    ..Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. ..
  14. Yuan B, Wan P, Chu D, Nie J, Cao Y, Luo W, et al. A cardiomyocyte-specific Wdr1 knockout demonstrates essential functional roles for actin disassembly during myocardial growth and maintenance in mice. Am J Pathol. 2014;184:1967-80 pubmed publisher
    ..Taken together, these results demonstrate that AIP1-regulated actin dynamics play essential roles in heart function in mice. ..
  15. Kos C, Le T, Sinha S, Henderson J, Kim S, Sugimoto H, et al. Mice deficient in alpha-actinin-4 have severe glomerular disease. J Clin Invest. 2003;111:1683-90 pubmed
    ..In addition, these genetic studies demonstrate that the nonsarcomeric alpha-actinin-4 is involved in the regulation of cell movement. ..
  16. Berman Y, North K. A gene for speed: the emerging role of alpha-actinin-3 in muscle metabolism. Physiology (Bethesda). 2010;25:250-9 pubmed publisher
    A common polymorphism (R577X) in the ACTN3 gene results in complete deficiency of alpha-actinin-3 protein in approximately 16% of humans worldwide...
  17. Garton F, Seto J, Quinlan K, Yang N, Houweling P, North K. ?-Actinin-3 deficiency alters muscle adaptation in response to denervation and immobilization. Hum Mol Genet. 2014;23:1879-93 pubmed publisher
    Homozygosity for a common null polymorphism (R577X) in the ACTN3 gene results in the absence of the fast fibre-specific protein, ?-actinin-3 in ?16% of humans worldwide...
  18. Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, et al. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest. 2005;115:1188-98 pubmed
    ..In concert, synaptopodin regulates the actin-bundling activity of alpha-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus. ..
  19. Nygren J, Liuba K, Breitbach M, Stott S, Thorén L, Roell W, et al. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol. 2008;10:584-92 pubmed publisher
    ..Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion hybrids, but almost exclusively in response to injuries or inflammation. ..
  20. Yang N, Schindeler A, McDonald M, Seto J, Houweling P, Lek M, et al. ?-Actinin-3 deficiency is associated with reduced bone mass in human and mouse. Bone. 2011;49:790-8 pubmed publisher
    ..Actinin-3 (ACTN3) is highly expressed in fast skeletal muscle fibres...
  21. Delgado Olguin P, Huang Y, Li X, Christodoulou D, Seidman C, Seidman J, et al. Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat Genet. 2012;44:343-7 pubmed publisher
    ..Our results suggest that epigenetic dysregulation in embryonic progenitor cells is a predisposing factor for adult disease and dysregulated stress responses. ..
  22. Houweling P, Berman Y, Turner N, Quinlan K, Seto J, Yang N, et al. Exploring the relationship between α-actinin-3 deficiency and obesity in mice and humans. Int J Obes (Lond). 2017;41:1154-1157 pubmed publisher
    ..A common null polymorphism in the fast fiber-specific gene ACTN3 (R577X) is known to influence skeletal muscle function and metabolism...
  23. Chan S, Seto J, MacArthur D, Yang N, North K, Head S. A gene for speed: contractile properties of isolated whole EDL muscle from an alpha-actinin-3 knockout mouse. Am J Physiol Cell Physiol. 2008;295:C897-904 pubmed publisher
    ..Homozygosity for a common polymorphism in the ACTN3 gene results in complete deficiency of alpha-actinin-3 in about 1 billion individuals worldwide...
  24. Beqqali A, Monshouwer Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, et al. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010;123:1141-50 pubmed publisher
    ..These findings suggest that CHAP is a critical component of the sarcomere with an important role in muscle development. ..
  25. Fernandes M, Lespinasse F, Rotomondo F, Poirier C, Guenet J, Gaudray P, et al. Comparative mapping of two adjacent regions of MMU19 with their human counterpart on HSA11q13. Cytogenet Cell Genet. 1998;81:237-46 pubmed
    ..5-Mb region. Strikingly, the 0.5-Mb region has a similar size in human but gene order is shuffled. The overall comparative map shows that these two regions are inverted on MMU19 when compared with HSA11q13. ..
  26. Hsu D, Guo Y, Alberts G, Peifley K, Winkles J. Fibroblast growth factor-1-inducible gene FR-17 encodes a nonmuscle alpha-actinin isoform. J Cell Physiol. 1996;167:261-8 pubmed
    ..These results indicate that nonmuscle alpha-actinin is a serum-, polypeptide growth factor-, and tumor promoter-inducible gene in mouse fibroblasts. ..
  27. North K. Why is alpha-actinin-3 deficiency so common in the general population? The evolution of athletic performance. Twin Res Hum Genet. 2008;11:384-94 pubmed publisher
    ..The human ACTN3 gene encodes the protein alpha-actinin-3, a component of the contractile apparatus in fast skeletal muscle fibers...
  28. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371-423 pubmed
    ..Both myosin and troponin isoforms contribute to the differences in the resistance to fatigue of muscle fibers...