Alpha-actinin-3

Last updated
ACTN3
Protein ACTN3 PDB 1tjt.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases ACTN3 , actinin alpha 3 (gene/pseudogene), ACTN3D, actinin alpha 3
External IDs OMIM: 102574 GeneCards: ACTN3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001104
NM_001258371

n/a

RefSeq (protein)

NP_001095
NP_001245300

n/a

Location (UCSC) Chr 11: 66.55 – 66.56 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

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 (named sprinter gene, speed gene or athlete gene) located on chromosome 11. All people have two copies (alleles) of this gene. [3] [4]

Contents

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. [5]

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. The alpha-actinin-3 protein is found in type II muscle fibers.

Alleles

An allele (rs1815739; 577X) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin-3 in the individuals. [6] [7] The X homozygous genotype (ACTN3 577XX) 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. [8] The 577XX polymorphism causes no production of alpha-actinin 3 protein which is essential in fast twitch muscle fibers. [8]

It has been speculated that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world. [6] :155–156 Over 75% of the persons have one or two copies of ACTN3 577R and have alpha-actinin-3. Homozygous individuals (ACTN3 577XX) have no alpha-actinin-3 (16%-20% of the population), [9] [10] but they have a high level of alpha-actinin-2.

Athletes

There is an association between the ACTN3 R577X polymorphism in sprint and powerlifting performance at an elite level (RR and RX variants are better), and appears to be an association with exercise recovery and lower injury risk. [8] It appears that the XX genotype is associated with higher levels of muscle damage and a longer time required for recovery. [8]

Interactions

ACTN3 has been shown to interact with alpha-actinin-2. [11]

See also

Related Research Articles

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<span class="mw-page-title-main">Actin, alpha skeletal muscle</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Actin, cytoplasmic 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Alpha-actinin-1</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.

<span class="mw-page-title-main">Alpha-actinin-2</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.

<span class="mw-page-title-main">Alpha-actinin-4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">FLNC (gene)</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TNNI2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TNNT1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MYOT</span> Mammalian protein found in Homo sapiens

Myotilin is a protein that in humans is encoded by the MYOT gene. Myotilin also known as TTID is a muscle protein that is found within the Z-disc of sarcomeres.

<span class="mw-page-title-main">MYL3</span> Protein-coding gene in the species Homo sapiens

Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.

<span class="mw-page-title-main">MYOZ2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">LDB3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MYOZ1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PDLIM3</span> Protein-coding gene in the species Homo sapiens

Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene. ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha-actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000248746 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "ACTN3 - Alpha-actinin-3 - Homo sapiens (Human) - ACTN3 gene & protein". www.uniprot.org. Retrieved 22 April 2022.
  4. 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): 9281–9288. doi: 10.1016/S0021-9258(19)50420-3 . PMID   1339456.
  5. "Entrez Gene: ACTN3 actinin, alpha 3".
  6. 1 2 Epstein D (2013). The Sports Gene: Inside the Science of Extraordinary Athletic Performance. Penguin. ISBN   978-1-101-62263-6.[ page needed ]
  7. 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): 353–354. doi:10.1038/7675. PMID   10192379. S2CID   19882092.
  8. 1 2 3 4 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.
  9. Hogarth MW, Houweling PJ, Thomas KC, Gordish-Dressman H, Bello L, Pegoraro E, et al. (January 2017). "Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy". Nature Communications. 8 (1): 14143. Bibcode:2017NatCo...814143H. doi:10.1038/ncomms14143. PMC   5290331 . PMID   28139640.
  10. Seto JT, Lek M, Quinlan KG, Houweling PJ, Zheng XF, Garton F, MacArthur DG, Raftery JM, Garvey SM, Hauser MA, Yang N, Head SI, North KN (2011). "Deficiency of α-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling". Human Molecular Genetics. 20 (15): 2914–2927. doi: 10.1093/hmg/ddr196 . PMID   21536590 . Retrieved 15 February 2022.
  11. 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): 134–139. doi:10.1006/bbrc.1998.8920. PMID   9675099.

Further reading