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ACTA2

Thursday 11 February 2010

actin, alpha 2, smooth muscle, aorta; AAT6; ACTSA; ACTA2

The protein encoded by ACTA2 gene belongs to the actin family of proteins, which are highly conserved proteins that play a role in cell motility, structure and integrity.

Actins (ACTss)

Six different actin isoforms have been identified in vertebrates by amino acid sequencing: skeletal muscle, cardiac muscle, 2 smooth muscle (enteric and aortic), and 2 cytoplasmic (beta and gamma).

Their amino acid sequences are similar and well conserved in evolution; e.g., skeletal and cardiac actins differ by only 4 amino acids, and skeletal muscle and cytoplasmic beta-actins differ by only 25 amino acids out of a total of 374.

Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. This actin is an alpha actin that is found in skeletal muscle.

Multiple alternatively spliced variants, encoding the same protein, have been identified.

GeneRIFs

- Integrin accelerates the synthesis of alpha-SMA in contracture of hypertrophic scar.

- findings confirm that ACTA2 mutations are important in familial TAAD, while the first sporadic and young-onset TAAD case with an ACTA2 mutation was also identified

- Mucosal remodeling with alterations of NCAM+ or alpha-SMA+ subepithelial and interstitial cells may play a critical role in UC-associated tumorigenesis.

- Observational study of gene-disease association. (HuGE Navigator)

- Alpha-SMA metabolism in basal cell carcinoma is associated with a more aggressive behaviour of this tumor.

- heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD

- TNF-alpha abrogated TGFbeta1-induced SMalphaA gene expression at the level of transcription without disrupting phosphorylation of regulatory Smads.

- These findings indicate the existence of alpha-smooth muscle actin-positive endothelial cells in adult aortic endothelium and the possible association with progression of atherosclerosis.

- Ezrin and alpha-smooth muscle actin are predictive immunohistochemical prognostic markers for patients with an osteosarcoma

- Study shows that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD).

- GATA-6 regulates human alpha-SMA expression via a novel regulatory cis element in the alpha-SMA promoter-enhancer

- Apha-smooth muscle actin may prove to be a valuable marker in the evaluation fibrosis progression and an early indicator of the development of fibrosis.

- Smooth muscle alpha-actin is expressed in endothelial cells derived from CD34+ human cord blood cells

- Human smooth muscle alpha-actin gene is a transcriptional target of the p53 tumor suppressor protein

Pathology

- Defects in this gene cause familial thoracic aortic aneurysm type 6 (AAT6). (MIM.611788)

- Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. (#19409525#)

References

- Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH, Pannu H, Willing MC, Sparks E, Pyeritz RE, Singh MN, Dalman RL, Grotta JC, Marian AJ, Boerwinkle EA, Frazier LQ, LeMaire SA, Coselli JS, Estrera AL, Safi HJ, Veeraraghavan S, Muzny DM, Wheeler DA, Willerson JT, Yu RK, Shete SS, Scherer SE, Raman CS, Buja LM, Milewicz DM. Am J Hum Genet. 2009 May;84(5):617-27. PMID: #19409525#