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UCSD-Nature Molecule Pages
Published online: 24 Jan 2006 | doi:10.1038/mp.a000196.01
Alpha-actinin-3
Cheri M Hampton1, Kenneth A Taylor1
1Institute of Molecular Biophysics, Florida State University, FL 32306-4380, US.
Correspondence should be addressed to Kenneth A Taylor: taylor@bio.fsu.edu
| Protein Function
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Based on high sequence identity to the other actinin isoforms and subcellular localization studies, the function of α-actinin-3 (Actn3) is to anchor actin filaments at the Z-disk. Its expression is limited to type 2B skeletal muscles fibers. It forms antiparallel homodimers or can form heterodimers with α-actinin-2 (Actn2). In human, the function of ACTN3 is overlapped by ACTN2, as evidenced by the lack of deleterious phenotype in ACTN3 null mutations. In mouse, however, these isoforms are not functionally redundant.
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| Regulation of Activity
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Protein activity is presumably regulated by competitive protein binding in the Z-disk.
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| Interactions with Ligands and Other Proteins
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Based on sequence identity and subcellular localization, Actn3 binds actin via its N-terminal actin binding domain which is composed of two tandem calponin homology domains.
Actn3 has been shown to associate with myozenin (FATZ, calsarcin) at Z-disks.
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| Regulation of Concentration
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No information is known about the regulation of concentration for Actn3.
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| Subcellular Localization
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Localized to Z-disks of type 2B skeletal muscle.
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| Major Sites of Expression
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Actn3 is only found in type 2B skeletal muscle (Beggs et al. 1992; Mills et al. 2001).
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| Phenotypes
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Approximately 18% of the human population carries a stop codon polymorphism (577X) resulting in a loss-of-function mutation that does not have a deleterious effect on phenotype. This is likely to be due to the functional redundancy of Actn2 which is also present in skeletal muscle sarcomeres, although this does not hold true in the mouse. Interestingly, the null mutation has been linked to a decrease in muscle power performance and increased endurance in olympic atheletes. More recent work has demonstrated that women with the 577X mutation have a reduced ability to produce high force strength, but develop dynamic strength in response to resistance training.
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| Splice Variants
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No information is known about any splice variants for Actn3.
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| Antibodies
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Mouse monoclonal antibody (mAb) to rabbit skeletal α-actinin, clone EA-53 (Sigma, abcam).
Mouse mAb to chicken gizzard actinin, clone JLN20 (ICN, InnoGenex, BioGenex, Oncogene Research Products).
Bovine mAb to mouse actinin, clone BM-75.2 (Sigma, ICN).
Mouse mAb to human actinin, clone AT 6/172 (Research Diagnostics Inc, Immune Systems Ltd).
Mouse mAb to quail smooth muscle actinin, 1E12 (Developmental Studies Hybridoma Bank at the University of Iowa).
Mouse mAb to chicken gizzard, clone CB11 (ICN, Affiniti).
Rabbit polyclonal Ab to chicken gizzard (ICN).
Mouse mAb to human red blood cell ghosts, clone RBC2/1B6 (Novocastra).
Mouse mAb to smooth muscle actinin, clone 1A4 (Diagnostic BioSystems).
Goat polyclonal Ab to aminoterminus of human ACTN1, N-19 (Santa Cruz Biotechnology).
Goat polyclonal Ab to human ACTN1 carboxyterminus, C-20 (Santa Cruz Biotechnology).
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| References |
| PM ID | Authors | Title | Journal | Pub Date |
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| 1339456 | Beggs AH, Byers TJ, Knoll JH, Boyce FM, Bruns GA, Kunkel LM | Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. | J Biol Chem,
267, 13 | 5 May 1992 |
| 15718405 | 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 | ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. | J Appl Physiol,
99, 1 | Jul 2005 |
| 12569417 | Dixson JD, Forstner MJ, Garcia DM | The alpha-actinin gene family: a revised classification. | J Mol Evol,
56, 1 | Jan 2003 |
| 11842093 | Frey N, Olson EN | Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins. | J Biol Chem,
277, 16 | 19 Apr 2002 |
| 15221860 | MacArthur DG, North KN | A gene for speed? The evolution and function of alpha-actinin-3. | Bioessays,
26, 7 | Jul 2004 |
| 11440986 | Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K | Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. | Hum Mol Genet,
10, 13 | 15 Jun 2001 |
| 15083532 | Otey CA, Carpen O | Alpha-actinin revisited: a fresh look at an old player. | Cell Motil Cytoskeleton,
58, 2 | Jun 2004 |
| 11171996 | Takada F, Vander Woude DL, Tong HQ, Thompson TG, Watkins SC, Kunkel LM, Beggs AH | Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines. | Proc Natl Acad Sci U S A,
98, 4 | 13 Feb 2001 |
| 15014165 | Virel A, Backman L | Molecular evolution and structure of alpha-actinin. | Mol Biol Evol,
21, 6 | Jun 2004 |
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