ACTG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5JLH
Identifiers
Aliases	ACTG1, ACT, ACTG, BRWS2, DFNA20, DFNA26, HEL-176, actin gamma 1
External IDs	OMIM: 102560; MGI: 87906; HomoloGene: 74402; GeneCards: ACTG1; OMA:ACTG1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q25.3 Start 81,509,413 bp[1] End 81,523,847 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 E2 Start 120,236,516 bp[2] End 120,239,368 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of ileum ventricular zone amniotic fluid embryo ganglionic eminence parietal pleura epithelium of nasopharynx visceral pleura spinal ganglia pericardium Top expressed in granulocyte ganglionic eminence neural tube Mesencephalon dentate gyrus of hippocampal formation granule cell placenta primary visual cortex epiblast blastocyst stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding ATP binding ubiquitin protein ligase binding identical protein binding structural constituent of cytoskeleton profilin binding Cellular component focal adhesion nucleus dense body cytoplasm membrane cytosol extracellular exosome blood microparticle plasma membrane cytoskeleton extracellular matrix extracellular space actin cytoskeleton myofibril filamentous actin myelin sheath actin filament Biological process cell junction assembly ephrin receptor signaling pathway platelet aggregation Fc-gamma receptor signaling pathway involved in phagocytosis retina homeostasis vascular endothelial growth factor receptor signaling pathway membrane organization sarcomere organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 71 11465 Ensembl ENSG00000184009 ENSMUSG00000062825 UniProt P63261 P63260 RefSeq (mRNA) NM_001199954 NM_001614 NM_009609 NM_001313923 RefSeq (protein) NP_001186883 NP_001605 NP_001300852 NP_033739 Location (UCSC) Chr 17: 81.51 – 81.52 Mb Chr 11: 120.24 – 120.24 Mb PubMed search [3] [4]
Wikidata
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Actin, cytoplasmic 2, or gamma-actin is a protein that in humans is encoded by the ACTG1 gene.^[5] 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.^[6] 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 paralogs, alpha, beta, and gamma, have been identified.^[7]

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.^[8][9][10]

In myocytes, sarcomeres adhere to the sarcolemma via costameres, which align at Z-discs and M-lines.^[11] The two primary cytoskeletal components of costameres are desmin intermediate filaments and gamma-actin microfilaments.^[12] It has been shown that gamma-actin interacting with another costameric protein dystrophin is critical for costameres forming mechanically strong links between the cytoskeleton and the sarcolemmal membrane.^[13][14] 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.^[15][16][17]

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.^[18] Gamma-actin is eventually replaced by sarcomeric alpha-actin isoforms,^[19][20][21] with low levels of gamma-actin persisting in adult myocytes which associate with Z-disc and costamere domains.^[15][22][23]

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.^[24]

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.^[25] Since then, other ACTG1 mutations have been linked to nonsyndromic hearing loss, including Met305Thr.^[26]

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.^[27][28]

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.^[29]

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.^[30]

ACTG1 has been shown to interact with:

• CAP1,^[31]
• DMD,^[13]
• TMSB4X,^[32][33] and
• Plectin.^[34]

• Actin

• Human ACTG1 genome location and ACTG1 gene details page in the UCSC Genome Browser.