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Actin gamma 1
Protein ACTG1 PDB 1atn.png
PDB rendering based on 1atn.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols ACTG1 ; ACT; ACTG; BRWS2; DFNA20; DFNA26; HEL-176
External IDs OMIM102560 MGI87906 HomoloGene74402 GeneCards: ACTG1 Gene
RNA expression pattern
PBB GE ACTG1 211983 x at tn.png
PBB GE ACTG1 201550 x at tn.png
PBB GE ACTG1 211970 x at tn.png
More reference expression data
Species Human Mouse
Entrez 71 11465
Ensembl ENSG00000184009 ENSMUSG00000062825
UniProt P63261 P63260
RefSeq (mRNA) NM_001199954 NM_009609
RefSeq (protein) NP_001186883 NP_033739
Location (UCSC) Chr 17:
81.51 – 81.52 Mb
Chr 11:
120.35 – 120.35 Mb
PubMed search [1] [2]

Gamma-actin is a protein that in humans is encoded by the ACTG1 gene.[1] Gamma-actin is widely expressed in cellular cytoskeletons of many tissues; in adult striated muscle cells, gamma-actin is localized to Z-discs and costamere structures, which are responsible for force transduction and transmission in muscle cells. Mutations in ACTG1 have been associated with nonsyndromic hearing loss and Baraitser-Winter syndrome, as well as susceptibility of adolescent patients to vincristine toxicity.


Human gamma-actin is 41.8 kDa in molecular weight and 375 amino acids in length.[2] Actins are highly conserved proteins that are involved in various types of cell motility, and maintenance of the cytoskeleton. In vertebrates, three main groups of actin isoforms, alpha, beta and gamma have been identified.[3]

The alpha actins are found in muscle tissues and are a major constituent of the sarcomere contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton, and as mediators of internal cell motility. Actin, gamma 1, encoded by this gene, is found in non-muscle cells in the cytoplasm, and in muscle cells at costamere structures, or transverse points of cell-cell adhesion that run perpendicular to the long axis of myocytes.[4][5][6]


In myocytes, sarcomeres adhere to the sarcolemma via costameres, which align at Z-discs and M-lines.[7] The two primary cytoskeletal components of costameres are desmin[disambiguation needed] intermediate filaments and gamma-actin microfilaments.[8] It has been shown that gamma-actin interacting with another costameric protein dystrophin[disambiguation needed] is critical for is critical for costameres forming mechanically strong links between the cytoskeleton and the sarcolemmal membrane.[9][10] Additional studies have shown that gamma-actin colocalizes with alpha-actinin and GFP-labeled gamma actin localized to Z-discs, whereas GFP-alpha-actin localized to pointed ends of thin filaments, indicating that gamma actin specifically localizes to Z-discs in striated muscle cells.[11][12][13]

During development of myocytes, gamma actin is thought to play a role in the organization and assembly of developing sarcomeres, evidenced in part by its early colocalization with alpha-actinin.[14] Gamma-actin is eventually replaced by sarcomeric alpha-actin isoforms,[15][16][17] with low levels of gamma-actin persisting in adult myocytes which associate with Z-disc and costamere domains.[18][19][20]

Insights into the function of gamma-actin in muscle have come from studies employing transgenesis. In a skeletal muscle-specific knockout of gamma-actin in mice, these animals showed no detectable abnormalities in development; however, knockout mice showed muscle weakness and fiber necrosis, along with decreased isometric twitch force, disrupted intrafibrillar and interfibrillar connections among myocytes, and myopathy.[21]

Clinical Significance[edit]

An autosomal dominant mutation in ACTG1 in the DFNA20/26 locus at 17q25-qter was identified in patients with hearing loss. A Thr278Ile mutation was identified in helix 9 of gamma-actin protein, which is predicted to alter protein structure. This study identified the first disease causing mutation in gamma-actin and underlies the importance of gamma-actin as structural elements of the inner ear hair cells.[22] Since then, other ACTG1 mutations have been linked to nonsyndromic hearing loss, including Met305Thr.[23]

A missense mutation in ACTG1 at Ser155Phe has also been identified in patients with Baraitser-Winter syndrome, which is a developmental disorder characterized by congenital ptosis, excessively-arched eyebrows, hypertelorism, ocular colobomata, lissencephaly, short stature, seizures and hearing loss.[24][25]

Differential expression of ACTG1 mRNA was also identified in patients with Sporadic Amyotrophic Lateral Sclerosis, a devastating disease with unknown causality, using a sophisticated bioinformatics approach employing Affymetrix long-oligonucleotide BaFL methods.[26]

Single nucleotide polymorphisms in ACTG1 have been associated with vincristine toxicity, which is part of the standard treatment regimen for childhood acute lymphoblastic leukemia. Neurotoxicity was more frequent in patients that were ACTG1 Gly310Ala mutation carriers, suggesting that this may play a role in patient outcomes from vincristine treatment.[27]


ACTG1 has been shown to interact with:

See also[edit]


  1. ^ "Entrez Gene: ACTG1 actin, gamma 1". 
  2. ^ "Protein sequence for human ACTG1 (Uniprot ID: P63261)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 18 July 2015. 
  3. ^ Rubenstein PA (Jul 1990). "The functional importance of multiple actin isoforms". BioEssays 12 (7): 309–15. doi:10.1002/bies.950120702. PMID 2203335. 
  4. ^ Craig SW, Pardo JV (1983). "Gamma actin, spectrin, and intermediate filament proteins colocalize with vinculin at costameres, myofibril-to-sarcolemma attachment sites". Cell Motility 3 (5-6): 449–62. PMID 6420066. 
  5. ^ Pardo JV, Siliciano JD, Craig SW (Feb 1983). "A vinculin-containing cortical lattice in skeletal muscle: transverse lattice elements ("costameres") mark sites of attachment between myofibrils and sarcolemma". Proceedings of the National Academy of Sciences of the United States of America 80 (4): 1008–12. PMID 6405378. 
  6. ^ Danowski BA, Imanaka-Yoshida K, Sanger JM, Sanger JW (Sep 1992). "Costameres are sites of force transmission to the substratum in adult rat cardiomyocytes". The Journal of Cell Biology 118 (6): 1411–20. PMID 1522115. 
  7. ^ Clark KA, McElhinny AS, Beckerle MC, Gregorio CC (2002). "Striated muscle cytoarchitecture: an intricate web of form and function". Annual Review of Cell and Developmental Biology 18: 637–706. doi:10.1146/annurev.cellbio.18.012502.105840. PMID 12142273. 
  8. ^ Kee AJ, Gunning PW, Hardeman EC (2009). "Diverse roles of the actin cytoskeleton in striated muscle". Journal of Muscle Research and Cell Motility 30 (5-6): 187–97. doi:10.1007/s10974-009-9193-x. PMID 19997772. 
  9. ^ Rybakova IN, Patel JR, Ervasti JM (Sep 2000). "The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin". The Journal of Cell Biology 150 (5): 1209–14. PMID 10974007. 
  10. ^ Ervasti JM (Apr 2003). "Costameres: the Achilles' heel of Herculean muscle". The Journal of Biological Chemistry 278 (16): 13591–4. doi:10.1074/jbc.R200021200. PMID 12556452. 
  11. ^ Nakata T, Nishina Y, Yorifuji H (Aug 2001). "Cytoplasmic gamma actin as a Z-disc protein". Biochemical and Biophysical Research Communications 286 (1): 156–63. doi:10.1006/bbrc.2001.5353. PMID 11485322. 
  12. ^ Papponen H, Kaisto T, Leinonen S, Kaakinen M, Metsikkö K (Jan 2009). "Evidence for gamma-actin as a Z disc component in skeletal myofibers". Experimental Cell Research 315 (2): 218–25. doi:10.1016/j.yexcr.2008.10.021. PMID 19013151. 
  13. ^ Vlahovich N, Kee AJ, Van der Poel C, Kettle E, Hernandez-Deviez D, Lucas C, Lynch GS, Parton RG, Gunning PW, Hardeman EC (Jan 2009). "Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle". Molecular Biology of the Cell 20 (1): 400–9. doi:10.1091/mbc.E08-06-0616. PMID 19005216. 
  14. ^ Lloyd CM, Berendse M, Lloyd DG, Schevzov G, Grounds MD (Jul 2004). "A novel role for non-muscle gamma-actin in skeletal muscle sarcomere assembly". Experimental Cell Research 297 (1): 82–96. doi:10.1016/j.yexcr.2004.02.012. PMID 15194427. 
  15. ^ Schwartz RJ, Rothblum KN (Jul 1981). "Gene switching in myogenesis: differential expression of the chicken actin multigene family". Biochemistry 20 (14): 4122–9. PMID 7284314. 
  16. ^ Shani M, Zevin-Sonkin D, Saxel O, Carmon Y, Katcoff D, Nudel U, Yaffe D (Sep 1981). "The correlation between the synthesis of skeletal muscle actin, myosin heavy chain, and myosin light chain and the accumulation of corresponding mRNA sequences during myogenesis". Developmental Biology 86 (2): 483–92. PMID 7286410. 
  17. ^ von Arx P, Bantle S, Soldati T, Perriard JC (Dec 1995). "Dominant negative effect of cytoplasmic actin isoproteins on cardiomyocyte cytoarchitecture and function". The Journal of Cell Biology 131 (6 Pt 2): 1759–73. PMID 8557743. 
  18. ^ Hanft LM, Bogan DJ, Mayer U, Kaufman SJ, Kornegay JN, Ervasti JM (Jul 2007). "Cytoplasmic gamma-actin expression in diverse animal models of muscular dystrophy". Neuromuscular Disorders 17 (7): 569–74. doi:10.1016/j.nmd.2007.03.004. PMID 17475492. 
  19. ^ Kee AJ, Schevzov G, Nair-Shalliker V, Robinson CS, Vrhovski B, Ghoddusi M, Qiu MR, Lin JJ, Weinberger R, Gunning PW, Hardeman EC (Aug 2004). "Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy". The Journal of Cell Biology 166 (5): 685–96. doi:10.1083/jcb.200406181. PMID 15337777. 
  20. ^ Nakata T, Nishina Y, Yorifuji H (Aug 2001). "Cytoplasmic gamma actin as a Z-disc protein". Biochemical and Biophysical Research Communications 286 (1): 156–63. doi:10.1006/bbrc.2001.5353. PMID 11485322. 
  21. ^ Sonnemann KJ, Fitzsimons DP, Patel JR, Liu Y, Schneider MF, Moss RL, Ervasti JM (Sep 2006). "Cytoplasmic gamma-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy". Developmental Cell 11 (3): 387–97. doi:10.1016/j.devcel.2006.07.001. PMID 16950128. 
  22. ^ van Wijk E, Krieger E, Kemperman MH, De Leenheer EM, Huygen PL, Cremers CW, Cremers FP, Kremer H (Dec 2003). "A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)". Journal of Medical Genetics 40 (12): 879–84. PMID 14684684. 
  23. ^ Park G, Gim J, Kim AR, Han KH, Kim HS, Oh SH, Park T, Park WY, Choi BY (18 March 2013). "Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family". BMC Genomics 14: 191. doi:10.1186/1471-2164-14-191. PMID 23506231. 
  24. ^ Rivière JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB (Apr 2012). "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome". Nature Genetics 44 (4): 440–4, S1–2. doi:10.1038/ng.1091. PMID 22366783. 
  25. ^ Di Donato N, Rump A, Koenig R, Der Kaloustian VM, Halal F, Sonntag K, Krause C, Hackmann K, Hahn G, Schrock E, Verloes A (Feb 2014). "Severe forms of Baraitser-Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations". European Journal of Human Genetics 22 (2): 179–83. doi:10.1038/ejhg.2013.130. PMID 23756437. 
  26. ^ Baciu C, Thompson KJ, Mougeot JL, Brooks BR, Weller JW (24 September 2012). "The LO-BaFL method and ALS microarray expression analysis". BMC Bioinformatics 13: 244. doi:10.1186/1471-2105-13-244. PMID 23006766. 
  27. ^ Ceppi F, Langlois-Pelletier C, Gagné V, Rousseau J, Ciolino C, De Lorenzo S, Kevin KM, Cijov D, Sallan SE, Silverman LB, Neuberg D, Kutok JL, Sinnett D, Laverdière C, Krajinovic M (Jun 2014). "Polymorphisms of the vincristine pathway and response to treatment in children with childhood acute lymphoblastic leukemia". Pharmacogenomics 15 (8): 1105–16. doi:10.2217/pgs.14.68. PMID 25084203. 
  28. ^ Hubberstey A, Yu G, Loewith R, Lakusta C, Young D (Jun 1996). "Mammalian CAP interacts with CAP, CAP2, and actin". Journal of Cellular Biochemistry 61 (3): 459–66. doi:10.1002/(SICI)1097-4644(19960601)61:3<459::AID-JCB13>3.0.CO;2-E. PMID 8761950. 
  29. ^ Rybakova IN, Patel JR, Ervasti JM (Sep 2000). "The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin". The Journal of Cell Biology 150 (5): 1209–14. PMID 10974007. 
  30. ^ Hertzog M, van Heijenoort C, Didry D, Gaudier M, Coutant J, Gigant B, Didelot G, Préat T, Knossow M, Guittet E, Carlier MF (May 2004). "The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to promotion of actin assembly". Cell 117 (5): 611–23. doi:10.1016/S0092-8674(04)00403-9. PMID 15163409. 
  31. ^ Van Troys M, Dewitte D, Goethals M, Carlier MF, Vandekerckhove J, Ampe C (Jan 1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis". The EMBO Journal 15 (2): 201–10. PMC 449934. PMID 8617195. 
  32. ^ Hijikata T, Nakamura A, Isokawa K, Imamura M, Yuasa K, Ishikawa R, Kohama K, Takeda S, Yorifuji H (Jun 2008). "Plectin 1 links intermediate filaments to costameric sarcolemma through beta-synemin, alpha-dystrobrevin and actin". Journal of Cell Science 121 (Pt 12): 2062–74. doi:10.1242/jcs.021634. PMID 18505798. 

Further reading[edit]